Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Highlights of the advances in basic immunology in 2011

Cellular & Molecular Immunology volume 9, pages 197–207 (2012)Cite this article

Abstract

In this review, we summarize the major fundamental advances in immunological research reported in 2011. The highlights focus on the improved understanding of key questions in basic immunology, including the initiation and activation of innate responses as well as mechanisms for the development and function of various T-cell subsets. The research includes the identification of novel cytosolic RNA and DNA sensors as well as the identification of the novel regulators of the Toll-like receptor (TLR) and retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) signaling pathway. Moreover, remarkable advances have been made in the developmental and functional properties of innate lymphoid cells (ILCs). Helper T cells and regulatory T (Treg) cells play indispensable roles in orchestrating adaptive immunity. There have been exciting discoveries regarding the regulatory mechanisms of the development of distinct T-cell subsets, particularly Th17 cells and Treg cells. The emerging roles of microRNAs (miRNAs) in T cell immunity are discussed, as is the recent identification of a novel T-cell subset referred to as follicular regulatory T (TFR) cells.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Medzhitov R, Janeway C Jr . Innate immunity. N Engl J Med 2000; 343: 338–344.

    CAS  PubMed  Google Scholar 

  2. Akira S, Uematsu S, Takeuchi O . Pathogen recognition and innate immunity. Cell 2006; 124: 783–801.

    Article  CAS  PubMed  Google Scholar 

  3. Paul WE, Seder RA . Lymphocyte responses and cytokines. Cell 1994; 76: 241–251.

    CAS  PubMed  Google Scholar 

  4. Janeway CA Jr, Medzhitov R . Innate immune recognition. Annu Rev Immunol 2002; 20: 197–216.

    CAS  PubMed  Google Scholar 

  5. Barbalat R, Ewald SE, Mouchess ML, Barton GM . Nucleic acid recognition by the innate immune system. Annu Rev Immunol 2011; 29: 185–214.

    CAS  PubMed  Google Scholar 

  6. Barton GM . Viral recognition by Toll-like receptors. Semin Immunol 2007; 19: 33–40.

    CAS  PubMed  Google Scholar 

  7. Yoneyama M, Kikuchi M, Natsukawa T, Shinobu N, Imaizumi T, Miyagishi M et al. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol 2004; 5: 730–737.

    CAS  PubMed  Google Scholar 

  8. Yoneyama M, Kikuchi M, Matsumoto K, Imaizumi T, Miyagishi M, Taira K et al. Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. J Immunol 2005; 175: 2851–2858.

    CAS  PubMed  Google Scholar 

  9. Sabbah A, Chang TH, Harnack R, Frohlich V, Tominaga K, Dube PH et al. Activation of innate immune antiviral responses by Nod2. Nat Immunol 2009; 10: 1073–1080.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Pichlmair A, Lassnig C, Eberle CA, Górna MW, Baumann CL, Burkard TR et al. IFIT1 is an antiviral protein that recognizes 5′-triphosphate RNA. Nat Immunol 2011; 12: 624–630.

    CAS  PubMed  Google Scholar 

  11. Pichlmair A, Schulz O, Tan CP, Näslund TI, Liljeström P, Weber F et al. RIG-I-mediated antiviral responses to single-stranded RNA bearing 5′-phosphates. Science 2006; 314: 997–1001.

    CAS  PubMed  Google Scholar 

  12. Hornung V, Ellegast J, Kim S, Brzózka K, Jung A, Kato H et al. 5′-Triphosphate RNA is the ligand for RIG-I. Science 2006; 314: 994–997.

    PubMed  Google Scholar 

  13. Ablasser A, Hornung V . Where, in antiviral defense, does IFIT1 fit? Nat Immunol 2011; 12: 588–590.

    CAS  PubMed  Google Scholar 

  14. Zhang Z, Kim T, Bao M, Facchinetti V, Jung SY, Ghaffari AA et al. DDX1, DDX21, and DHX36 helicases form a complex with the adaptor molecule TRIF to sense dsRNA in dendritic cells. Immunity 2011; 34: 866–878.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Zhang Z, Yuan B, Lu N, Facchinetti V, Liu YJ . DHX9 pairs with IPS-1 to sense double-stranded RNA in myeloid dendritic cells. J Immunol 2011; 187: 4501–4508.

    CAS  PubMed  Google Scholar 

  16. Luo D, Ding SC, Vela A, Kohlway A, Lindenbach BD, Pyle AM . Structural insights into RNA recognition by RIG-I. Cell 2011; 147: 409–422.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Kowalinski E, Lunardi T, McCarthy AA, Louber J, Brunel J, Grigorov B et al. Structural basis for the activation of innate immune pattern-recognition receptor RIG-I by viral RNA. Cell 2011; 147: 423–435.

    CAS  PubMed  Google Scholar 

  18. Jiang F, Ramanathan A, Miller MT, Tang GQ, Gale M, Patel SS et al. Structural basis of RNA recognition and activation by innate immune receptor RIG-I. Nature 2011; 479: 423–427.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Daffis S, Szretter KJ, Schriewer J, Li J, Youn S, Errett J et al. 2′-O methylation of the viral mRNA cap evades host restriction by IFIT family members. Nature 2010; 468: 452–456.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Züst R, Cervantes-Barragan L, Habjan M, Maier R, Neuman BW, Ziebuhr J et al. Ribose 2′-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5. Nat Immunol 2011; 12: 137–143.

    PubMed  PubMed Central  Google Scholar 

  21. García-Sastre A . 2 methylate or not 2 methylate: viral evasion of the type I interferon response. Nat Immunol 2011; 12: 114–115.

    PubMed  PubMed Central  Google Scholar 

  22. Takaoka A, Wang Z, Choi MK, Yanai H, Negishi H, Ban T et al. DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response. Nature 2007; 448: 501–505.

    CAS  PubMed  Google Scholar 

  23. Fernandes-Alnemri T, Yu JW, Datta P, Wu J, Alnemri ES . AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature 2009; 458: 509–513.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Hornung V, Ablasser A, Charrel-Dennis M, Bauernfeind F, Horvath G, Caffrey DR et al. AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature 2009; 458: 514–518.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Bürckstümmer T, Baumann C, Blüml S, Dixit E, Dürnberger G, Jahn H et al. An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome. Nat Immunol 2009; 10: 266–272.

    PubMed  Google Scholar 

  26. Chiu YH, Macmillan JB, Chen ZJ . RNA polymerase III detects cytosolic DNA and induces type I interferons through the RIG-I pathway. Cell 2009; 138: 576–591.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Ablasser A, Bauernfeind F, Hartmann G, Latz E, Fitzgerald KA, Hornung V . RIG-I-dependent sensing of poly(dA:dT) through the induction of an RNA polymerase III-transcribed RNA intermediate. Nat Immunol 2009; 10: 1065–1072.

    CAS  PubMed  Google Scholar 

  28. Cao X . New DNA-sensing pathway feeds RIG-I with RNA. Nat Immunol 2009; 10: 1049–1051.

    CAS  PubMed  Google Scholar 

  29. Unterholzner L, Keating SE, Baran M, Horan KA, Jensen SB, Sharma S et al. IFI16 is an innate immune sensor for intracellular DNA. Nat Immunol 2010; 11: 997–1004.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Zhang Z, Yuan B, Bao M, Lu N, Kim T, Liu YJ . The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cells. Nat Immunol 2011; 12: 959–965.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Zhang X, Brann TW, Zhou M, Yang J, Oguariri RM, Lidie KB et al. Cutting edge: Ku70 is a novel cytosolic DNA sensor that induces type III rather than type I IFN. J Immunol 2011; 186: 4541–4545.

    CAS  PubMed  Google Scholar 

  32. Barber GN . STING-dependent signaling. Nat Immunol 2011; 12: 929–930.

    CAS  PubMed  Google Scholar 

  33. Yang P, An H, Liu X, Wen M, Zheng Y, Rui Y et al. The cytosolic nucleic acid sensor LRRFIP1 mediates the production of type I interferon via a beta-catenin-dependent pathway. Nat Immunol 2010; 11: 487–494.

    CAS  PubMed  Google Scholar 

  34. Akira S, Takeda K . Toll-like receptor signalling. Nat Rev Immunol 2004; 4: 499–511.

    CAS  PubMed  Google Scholar 

  35. Wang C, Chen T, Zhang J, Yang M, Li N, Xu X et al. The E3 ubiquitin ligase Nrdp1 ‘preferentially’ promotes TLR-mediated production of type I interferon. Nat Immunol 2009; 10: 744–752.

    CAS  PubMed  Google Scholar 

  36. Liu X, Zhan Z, Li D, Xu L, Ma F, Zhang P et al. Intracellular MHC class II molecules promote TLR-triggered innate immune responses by maintaining activation of the kinase Btk. Nat Immunol 2011; 12: 416–424.

    CAS  PubMed  Google Scholar 

  37. Hassan GS, Mourad W . An unexpected role for MHC class II. Nat Immunol 2011; 12: 375–376.

    CAS  PubMed  Google Scholar 

  38. Tun-Kyi A, Finn G, Greenwood A, Nowak M, Lee TH, Asara JM et al. Essential role for the prolyl isomerase Pin1 in Toll-like receptor signaling and type I interferon-mediated immunity. Nat Immunol 2011; 12: 733–741.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Saitoh T, Satoh T, Yamamoto N, Uematsu S, Takeuchi O, Kawai T et al. Antiviral protein Viperin promotes Toll-like receptor 7- and Toll-like receptor 9-mediated type I interferon production in plasmacytoid dendritic cells. Immunity 2011; 34: 352–363.

    CAS  PubMed  Google Scholar 

  40. Liew FY, Xu D, Brint EK, O'Neill LA . Negative regulation of toll-like receptor-mediated immune responses. Nat Rev Immunol 2005; 5: 446–458.

    CAS  PubMed  Google Scholar 

  41. Lee EG, Boone DL, Chai S, Libby SL, Chien M, Lodolce JP et al. Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice. Science 2000; 289: 2350–2354.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Kobayashi K, Hernandez LD, Galán JE, Janeway CA Jr, Medzhitov R, Flavell RA . IRAK-M is a negative regulator of Toll-like receptor signaling. Cell 2002; 110: 191–202.

    CAS  PubMed  Google Scholar 

  43. Nakagawa R, Naka T, Tsutsui H, Fujimoto M, Kimura A, Abe T et al. SOCS-1 participates in negative regulation of LPS responses. Immunity 2002; 17: 677–687.

    CAS  PubMed  Google Scholar 

  44. Wald D, Qin J, Zhao Z, Qian Y, Naramura M, Tian L et al. SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling. Nat Immunol 2003; 4: 920–927.

    CAS  PubMed  Google Scholar 

  45. Brint EK, Xu D, Liu H, Dunne A, McKenzie AN, O'Neill LA et al. ST2 is an inhibitor of interleukin 1 receptor and Toll-like receptor 4 signaling and maintains endotoxin tolerance. Nat Immunol 2004; 5: 373–379.

    CAS  PubMed  Google Scholar 

  46. Kawagoe T, Takeuchi O, Takabatake Y, Kato H, Isaka Y, Tsujimura T et al. TANK is a negative regulator of Toll-like receptor signaling and is critical for the prevention of autoimmune nephritis. Nat Immunol 2009; 10: 965–972.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Han C, Jin J, Xu S, Liu H, Li N, Cao X . Integrin CD11b negatively regulates TLR-triggered inflammatory responses by activating Syk and promoting degradation of MyD88 and TRIF via Cbl-b. Nat Immunol 2010; 11: 734–742.

    CAS  PubMed  Google Scholar 

  48. Yuk JM, Shin DM, Lee HM, Kim JJ, Kim SW, Jin HS et al. The orphan nuclear receptor SHP acts as a negative regulator in inflammatory signaling triggered by Toll-like receptors. Nat Immunol 2011; 12: 742–751.

    CAS  PubMed  Google Scholar 

  49. Beyaert R . SHP works a double shift to control TLR signaling. Nat Immunol 2011; 12: 725–727.

    CAS  PubMed  Google Scholar 

  50. Kufer TA, Sansonetti PJ . NLR functions beyond pathogen recognition. Nat Immunol 2011; 12: 121–128.

    CAS  PubMed  Google Scholar 

  51. Xia X, Cui J, Wang HY, Zhu L, Matsueda S, Wang Q et al. NLRX1 negatively regulates TLR-induced NF-κB signaling by targeting TRAF6 and IKK. Immunity 2011; 34: 843–853.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Allen IC, Moore CB, Schneider M, Lei Y, Davis BK, Scull MA et al. NLRX1 protein attenuates inflammatory responses to infection by interfering with the RIG-I–MAVS and TRAF6–NF-κB signaling pathways. Immunity 2011; 34: 854–865.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Chevrier N, Mertins P, Artyomov MN, Shalek AK, Iannacone M, Ciaccio MF et al. Systematic discovery of TLR signaling components delineates viral-sensing circuits. Cell 2011; 147: 853–867.

    CAS  PubMed  Google Scholar 

  54. Loo YM, Gale M Jr . Immune signaling by RIG-I-like receptors. Immunity 2011; 34: 680–692.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Ramos HJ, Gale M Jr . RIG-I like receptors and their signaling crosstalk in the regulation of antiviral immunity. Curr Opin Virol 2011; 1: 167–176.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Hayakawa S, Shiratori S, Yamato H, Kameyama T, Kitatsuji C, Kashigi F et al. ZAPS is a potent stimulator of signaling mediated by the RNA helicase RIG-I during antiviral responses. Nat Immunol 2011; 12: 37–44.

    CAS  PubMed  Google Scholar 

  57. McWhirter SM, Tenoever BR, Maniatis T . Connecting mitochondria and innate immunity. Cell 2005; 122: 645–647.

    CAS  PubMed  Google Scholar 

  58. Gack MU, Shin YC, Joo CH, Urano T, Liang C, Sun L et al. TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. Nature 2007; 446: 916–920.

    CAS  PubMed  Google Scholar 

  59. Ishikawa H, Barber GN . STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature 2008; 455: 674–678.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Okabe Y, Sano T, Nagata S . Regulation of the innate immune response by threonine-phosphatase of Eyes absent. Nature 2009; 460: 520–524.

    CAS  PubMed  Google Scholar 

  61. Hou F, Sun L, Zheng H, Skaug B, Jiang QX, Chen ZJ . MAVS forms function al prion-like aggregates to activate and propagate antiviral innate immune response. Cell 2011; 146: 448–461.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Chen H, Sun H, You F, Sun W, Zhou X, Chen L et al. Activation of STAT6 by STING is critical for antiviral innate immunity. Cell 2011; 147: 436–446.

    CAS  PubMed  Google Scholar 

  63. Spits H, Di Santo JP . The expanding family of innate lymphoid cells: regulators and effectors of immunity and tissue remodeling. Nat Immunol 2011; 12: 21–27 .

    CAS  PubMed  Google Scholar 

  64. Gascoyne DM, Long E, Veiga-Fernandes H, de Boer J, Williams O, Seddon B et al. The basic leucine zipper transcription factor E4BP4 is essential for natural killer cell development. Nat Immunol 2009; 10: 1118–1124.

    CAS  PubMed  Google Scholar 

  65. Eberl G, Marmon S, Sunshine MJ, Rennert PD, Choi Y, Littman DR . An essential function for the nuclear receptor RORγt in the generation of fetal lymphoid tissue inducer cells. Nat Immunol 2004; 5: 64–73.

    CAS  PubMed  Google Scholar 

  66. Possot C, Schmutz S, Chea S, Boucontet L, Louise A, Cumano A et al. Notch signaling is necessary for adult, but not fetal, development of RORγt+ innate lymphoid cells. Nat Immunol 2011; 12: 949–958.

    CAS  PubMed  Google Scholar 

  67. Lee JS, Cella M, McDonald KG, Garlanda C, Kennedy GD, Nukaya M et al. AHR drives the development of gut ILC22 cells and postnatal lymphoid tissues via pathways dependent on and independent of Notch. Nat Immunol 2012; 13: 144–151.

    CAS  Google Scholar 

  68. Quintana FJ, Basso AS, Iglesias AH, Korn T, Farez MF, Bettelli E et al. Control of Treg and TH17 cell differentiation by the aryl hydrocarbon receptor. Nature 2008; 453: 65–71.

    CAS  PubMed  Google Scholar 

  69. Trifari S, Kaplan CD, Tran EH, Crellin NK, Spits H . Identification of a human helper T cell population that has abundant production of interleukin 22 and is distinct from TH-17, TH1 and TH)2 cells. Nat Immunol 2009; 10: 864–871.

    CAS  PubMed  Google Scholar 

  70. Cella M, Fuchs A, Vermi W, Facchetti F, Otero K, Lennerz JK et al. A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity. Nature 2009; 457: 722–725.

    CAS  PubMed  Google Scholar 

  71. Kiss EA, Vonarbourg C, Kopfmann S, Hobeika E, Finke D, Esser C et al. Natural Aryl hydrocarbon receptor ligands control organogenesis of intestinal lymphoid follicles. Science 2011; 334: 1561–1565.

    CAS  PubMed  Google Scholar 

  72. Li Y, Innocentin S, Withers DR, Roberts NA, Gallagher AR, Grigorieva EF et al. Exogenous stimuli maintain intraepithelial lymphocytes via aryl hydrocarbon receptor activation. Cell 2011; 147: 629–640.

    CAS  PubMed  Google Scholar 

  73. Sawa S, Lochner M, Satoh-Takayama N, Dulauroy S, Bérard M, Kleinschek M et al. RORγt+ innate lymphoid cells regulate intestinal homeostasis by integrating negative signals from the symbiotic microbiota. Nat Immunol 2011; 12: 320–326.

    CAS  PubMed  Google Scholar 

  74. Monticelli LA, Sonnenberg GF, Abt MC, Alenghat T, Ziegler CG, Doering TA et al. Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus. Nat Immunol 2011; 12: 1045–1054.

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Wills-Karp M, Finkelman FD . Innate lymphoid cells wield a double-edged sword. Nat Immunol 2011; 12: 1025–1027.

    CAS  PubMed  Google Scholar 

  76. Mjösberg JM, Trifari S, Crellin NK, Peters CP, van Drunen CM, Piet B et al. Human IL-25- and IL-33-responsive type 2 innate lymphoid cells are defined by expression of CRTH2 and CD161. Nat Immunol 2011; 12: 1055–1062.

    PubMed  Google Scholar 

  77. Chang YJ, Kim HY, Albacker LA, Baumgarth N, McKenzie AN, Smith DE et al. Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity. Nat Immunol 2011; 12: 631–638.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Bordon Y . Asthma and allergy: influenza virus and an innate form of asthma. Nat Rev Immunol 2011; 11: 443.

    CAS  PubMed  Google Scholar 

  79. Cormier SA, Kolls JK . Innate IL-13 in virus-induced asthma? Nat Immunol 2011; 12: 587–588.

    CAS  PubMed  Google Scholar 

  80. Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL . Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 1986; 136: 2348–2357.

    CAS  PubMed  Google Scholar 

  81. Mosmann TR, Coffman RL . TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 1989; 7: 145–173.

    CAS  PubMed  Google Scholar 

  82. Korn T, Bettelli E, Oukka M, Kuchroo VK . IL-17 and Th17 cells. Annu Rev Immunol 2009; 27: 485–517.

    CAS  PubMed  Google Scholar 

  83. Sakaguchi S, Yamaguchi T, Nomura T, Ono M . Regulatory T cells and immune tolerance. Cell 2008; 133: 775–787.

    CAS  PubMed  Google Scholar 

  84. O'Shea JJ, Paul WE . Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells. Science 2010; 327: 1098–1102.

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Pai SY, Truitt ML, Ho IC . GATA-3 deficiency abrogates the development and maintenance of T helper type 2 cells. Proc Natl Acad Sci USA 2004; 101: 1993–1998.

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Yamashita M, Ukai-Tadenuma M, Miyamoto T, Sugaya K, Hosokawa H, Hasegawa A et al. Essential role of GATA3 for the maintenance of type 2 helper T (Th2) cytokine production and chromatin remodeling at the Th2 cytokine gene loci. J Biol Chem 2004; 279: 26983–26990.

    CAS  PubMed  Google Scholar 

  87. Tanaka S, Motomura Y, Suzuki Y, Yagi R, Inoue H, Miyatake S et al. The enhancer HS2 critically regulates GATA-3-mediated Il4 transcription in TH2 cells. Nat Immunol 2011; 12: 77–85.

    CAS  PubMed  Google Scholar 

  88. van Stry M, Bix M . Explaining discordant coordination. Nat Immunol 2011; 12: 16–17.

    CAS  PubMed  Google Scholar 

  89. Leavy O . T cells: shaping Il4 gene expression. Nat Rev Immunol 2011; 11: 3.

    CAS  PubMed  Google Scholar 

  90. Kool M, Willart MA, van Nimwegen M, Bergen I, Pouliot P, Virchow JC et al. An unexpected role for uric acid as an inducer of T helper 2 cell immunity to inhaled antigens and inflammatory mediator of allergic asthma. Immunity 2011; 34: 527–540.

    CAS  PubMed  Google Scholar 

  91. Kuroda E, Ishii KJ, Uematsu S, Ohata K, Coban C, Akira S et al. Silica crystals and aluminum salts regulate the production of prostaglandin in macrophages via NALP3 inflammasome-independent mechanisms. Immunity 2011; 34: 514–526.

    CAS  PubMed  Google Scholar 

  92. Eisenbarth SC, Colegio OR, O'Connor W, Sutterwala FS, Flavell RA . Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants. Nature 2008; 453: 1122–1126.

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Pelka K, Latz E . Getting closer to the dirty little secret. Immunity 2011; 34: 455–458.

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Bordon Y . Allergy: crystal clear culprit. Nat Rev Immunol 2011; 11: 304.

    CAS  PubMed  Google Scholar 

  95. Islam SA, Chang DS, Colvin RA, Byrne MH, McCully ML, Moser B et al. Mouse CCL8, a CCR8 agonist, promotes atopic dermatitis by recruiting IL-5+ TH2 cells. Nat Immunol 2011; 12: 167–177.

    CAS  PubMed  Google Scholar 

  96. Debes GF, Diehl MC . CCL8 and skin T cells—an allergic attraction. Nat Immunol 2011; 12: 111–112.

    CAS  PubMed  Google Scholar 

  97. Li Z, Zhang Y, Liu Z, Wu X, Zheng Y, Tao Z et al. ECM1 controls TH2 cell egress from lymph nodes through re-expression of S1P1. Nat Immunol 2011; 12: 178–185.

    CAS  PubMed  Google Scholar 

  98. Bordon Y . Lymphocyte migration: travel agents for two. Nat Rev Immunol 2011; 11: 77.

    CAS  PubMed  Google Scholar 

  99. Martinez GJ, Nurieva RI, Yang XO, Dong C . Regulation and function of proinflammatory TH17 cells. Ann NY Acad Sci 2008; 1143: 188–211.

    CAS  PubMed  Google Scholar 

  100. Ivanov II, Zhou L, Littman DR . Transcriptional regulation of Th17 cell differentiation. Semin Immunol 2007; 19: 409–417.

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Dang EV, Barbi J, Yang HY, Jinasena D, Yu H, Zheng Y et al. Control of TH17/Treg balance by hypoxia-inducible factor 1. Cell 2011; 146: 772–784.

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Nutsch K, Hsieh C . When T cells run out of breath: the HIF-1α story. Cell 2011; 146: 673–674.

    CAS  PubMed  Google Scholar 

  103. Lazarevic V, Chen X, Shim JH, Hwang ES, Jang E, Bolm AN et al. T-bet represses TH17 differentiation by preventing Runx1-mediated activation of the gene encoding RORγt. Nat Immunol 2011; 12: 96–104.

    CAS  PubMed  Google Scholar 

  104. Yang XP, Ghoreschi K, Steward-Tharp SM, Rodriguez-Canales J, Zhu J, Grainger JR et al. Opposing regulation of the locus encoding IL-17 through direct, reciprocal actions of STAT3 and STAT5. Nat Immunol 2011; 12: 247–254.

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Cao W, Yang Y, Wang Z, Liu A, Fang L, Wu F et al. Leukemia inhibitory factor inhibits T helper 17 cell differentiation and confers treatment effects of neural progenitor cell therapy in autoimmune disease. Immunity 2011; 35: 273–284.

    CAS  PubMed  Google Scholar 

  106. Awasthi A, Kuchroo VK . Value added: neural progenitor cells suppress inflammation and autoimmunity. Immunity 2011; 35: 156–157.

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Solt LA, Kumar N, Nuhant P, Wang Y, Lauer JL, Liu J et al. Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand. Nature 2011; 472: 491–494.

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Jetten AM . Immunology: a helping hand against autoimmunity. Nature 2011; 472: 421–422.

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 2005; 201: 233–240.

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Codarri L, Gyülvészi G, Tosevski V, Hesske L, Fontana A, Magnenat L et al. RORγt drives production of the cytokine GM-CSF in helper T cells, which is essential for the effector phase of autoimmune neuroinflammation. Nat Immunol 2011; 12: 560–567.

    CAS  PubMed  Google Scholar 

  111. El-Behi M, Ciric B, Dai H, Yan Y, Cullimore M, Safavi F et al. The encephalitogenicity of TH17 cells is dependent on IL-1- and IL-23-induced production of the cytokine GM-CSF. Nat Immunol 2011; 12: 568–575.

    CAS  PubMed  PubMed Central  Google Scholar 

  112. McGeachy MJ . GM-CSF: the secret weapon in the TH17 arsenal. Nat Immunol 2011; 12: 521–522.

    CAS  PubMed  Google Scholar 

  113. Xu S, Cao X . Interleukin-17 and its expanding biological functions. Cell Mol Immunol 2010; 7: 164–174.

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Song X, Zhu S, Shi P, Liu Y, Shi Y, Levin SD et al. IL-17RE is the functional receptor for IL-17C and mediates mucosal immunity to infection with intestinal pathogens. Nat Immunol 2011; 12: 1151–1158.

    CAS  PubMed  Google Scholar 

  115. Ramirez-Carrozzi V, Sambandam A, Luis E, Lin Z, Jeet S, Lesch J et al. IL-17C regulates the innate immune function of epithelial cells in an autocrine manner. Nat Immunol 2011; 12: 1159–1166.

    CAS  PubMed  Google Scholar 

  116. Swamy M, Hayday A . Provocative exhibits at the Seventeen Gallery. Nat Immunol 2011; 12: 1131–1133.

    CAS  PubMed  Google Scholar 

  117. Chang SH, Reynolds JM, Pappu BP, Chen G, Martinez GJ, Dong C . Interleukin-17C promotes Th17 cell responses and autoimmune disease via interleukin-17 receptor E. Immunity 2011; 35: 611–621.

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Martinez GJ, Nurieva RI, Yang XO, Dong C . Regulation and function of proinflammatory TH17 cells. Ann NY Acad Sci 2008; 1143: 188–211.

    CAS  PubMed  Google Scholar 

  119. Sakaguchi S . Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol 2004; 22: 531–562.

    CAS  PubMed  Google Scholar 

  120. Bluestone JA, Abbas AK . Natural versus adaptive regulatory T cells. Nat Rev Immunol 2003; 3: 253–257.

    CAS  PubMed  Google Scholar 

  121. Fontenot JD, Gavin MA, Rudensky AY . Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 2003; 4: 330–336.

    CAS  PubMed  Google Scholar 

  122. Cretney E, Xin A, Shi W, Minnich M, Masson F, Miasari M et al. The transcription factors Blimp-1 and IRF4 jointly control the differentiation and function of effector regulatory T cells. Nat Immunol 2011; 12: 304–311.

    CAS  PubMed  Google Scholar 

  123. Ohkura N, Sakaguchi S . Maturation of effector regulatory T cells. Nat Immunol 2011; 12: 283–284.

    CAS  PubMed  Google Scholar 

  124. Maruyama T, Li J, Vaque JP, Konkel JE, Wang W, Zhang B et al. Control of the differentiation of regulatory T cells and TH17 cells by the DNA-binding inhibitor Id3. Nat Immunol 2011; 12: 86–95.

    CAS  PubMed  Google Scholar 

  125. Tone M, Greene MI . Cooperative regulatory events and Foxp3 expression. Nat Immunol 2011; 12: 14–16.

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Wang Y, Su MA, Wan YY . An essential role of the transcription factor GATA-3 for the function of regulatory T cells. Immunity 2011; 35: 337–348.

    CAS  PubMed  PubMed Central  Google Scholar 

  127. Mantel PY, Kuipers H, Boyman O, Rhyner C, Ouaked N, Rückert B et al. GATA3-driven Th2 responses inhibit TGF-beta1-induced FOXP3 expression and the formation of regulatory T cells. PLoS Biol 2007; 5: e329.

    PubMed  PubMed Central  Google Scholar 

  128. Campbell DJ . Regulatory T cells GATA have it. Immunity 2011; 35: 313–315.

    CAS  PubMed  Google Scholar 

  129. Beal AM, Ramos-Hernández N, Riling CR, Nowelsky EA, Oliver PM . TGF-β induces the expression of the adaptor Ndfip1 to silence IL-4 production during iTreg cell differentiation. Nat Immunol 2012; 13: 77–85.

    CAS  Google Scholar 

  130. Beyer M, Thabet Y, Müller RU, Sadlon T, Classen S, Lahl K et al. Repression of the genome organizer SATB1 in regulatory T cells is required for suppressive function and inhibition of effector differentiation. Nat Immunol 2011; 12: 898–907.

    CAS  PubMed  PubMed Central  Google Scholar 

  131. King C . New insights into the differentiation and function of T follicular helper cells. Nat Rev Immunol 2009; 9: 757–766.

    CAS  PubMed  Google Scholar 

  132. Nurieva RI, Chung Y, Hwang D, Yang XO, Kang HS, Ma L et al. Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages. Immunity 2008; 29: 138–149.

    CAS  PubMed  PubMed Central  Google Scholar 

  133. King C, Tangye SG, Mackay CR . T follicular helper (TFH) cells in normal and dysregulated immune responses. Annu Rev Immunol 2008; 26: 741–766.

    CAS  PubMed  Google Scholar 

  134. Yu D, Rao S, Tsai LM, Lee SK, He Y, Sutcliffe EL et al. The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment. Immunity 2009; 31: 457–468.

    CAS  PubMed  Google Scholar 

  135. Nurieva RI, Chung Y, Martinez GJ, Yang XO, Tanaka S, Matskevitch TD et al. Bcl6 mediates the development of T follicular helper cells. Science 2009; 325: 1001–1005.

    CAS  PubMed  PubMed Central  Google Scholar 

  136. Johnston RJ, Poholek AC, DiToro D, Yusuf I, Eto D, Barnett B et al. Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation. Science 2009; 325: 1006–1010.

    CAS  PubMed  PubMed Central  Google Scholar 

  137. Bauquet AT, Jin H, Paterson AM, Mitsdoerffer M, Ho IC, Sharpe AH et al. The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and TH-17 cells. Nat Immunol 2009; 10: 167–175.

    CAS  PubMed  Google Scholar 

  138. Pelletier N, McHeyzer-Williams LJ, Wong KA, Urich E, Fazilleau N, McHeyzer-Williams MG . Plasma cells negatively regulate the follicular helper T cell program. Nat Immunol 2010; 11: 1110–1118.

    CAS  PubMed  PubMed Central  Google Scholar 

  139. Morita R, Schmitt N, Bentebibel SE, Ranganathan R, Bourdery L, Zurawski G et al. Human blood CXCR5+CD4+ T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion. Immunity 2011; 34: 108–121.

    CAS  PubMed  PubMed Central  Google Scholar 

  140. Koch MA, Tucker-Heard G, Perdue NR, Killebrew JR, Urdahl KB, Campbell DJ . The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammation. Nat Immunol 2009; 10: 595–602.

    CAS  PubMed  PubMed Central  Google Scholar 

  141. Zheng Y, Chaudhry A, Kas A, deRoos P, Kim JM, Chu TT et al. Regulatory T-cell suppressor program co-opts transcription factor IRF4 to control TH2 responses. Nature 2009; 458: 351–356.

    CAS  PubMed  PubMed Central  Google Scholar 

  142. Chaudhry A, Rudra D, Treuting P, Samstein RM, Liang Y, Kas A et al. CD4+ regulatory T cells control TH17 responses in a Stat3-dependent manner. Science 2009; 326: 986–991.

    CAS  PubMed  PubMed Central  Google Scholar 

  143. Linterman MA, Pierson W, Lee SK, Kallies A, Kawamoto S, Rayner TF et al. Foxp3+ follicular regulatory T cells control the germinal center response. Nat Med 2011; 17: 975–982.

    CAS  PubMed  PubMed Central  Google Scholar 

  144. Chung Y, Tanaka S, Chu F, Nurieva RI, Martinez GJ, Rawal S et al. Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions. Nat Med 2011; 17: 983–988.

    CAS  PubMed  PubMed Central  Google Scholar 

  145. Wollenberg I, Agua-Doce A, Hernández A, Almeida C, Oliveira VG, Faro J et al. Regulation of the germinal center reaction by foxp3+ follicular regulatory T cells. J Immunol 2011; 187: 4553–4560.

    CAS  PubMed  Google Scholar 

  146. Papatriantafyllou M . Regulatory T cells: pursuing a germinal centre career. Nat Rev Immunol 2011; 11: 572.

    PubMed  Google Scholar 

  147. Campbell DJ, Koch MA . Treg cells cells: patrolling a dangerous neighborhood. Nat Med 2011; 17: 929–930.

    CAS  PubMed  Google Scholar 

  148. Yang CY, Best JA, Knell J, Yang E, Sheridan AD, Jesionek AK et al. The transcriptional regulators Id2 and Id3 control the formation of distinct memory CD8+ T cell subsets. Nat Immunol 2011; 12: 1221–1229.

    CAS  PubMed  Google Scholar 

  149. Ji Y, Pos Z, Rao M, Klebanoff CA, Yu Z, Sukumar M et al. Repression of the DNA-binding inhibitor Id3 by Blimp-1 limits the formation of memory CD8+ T cells. Nat Immunol 2011; 12: 1230–2137.

    CAS  PubMed  PubMed Central  Google Scholar 

  150. Araki K, Turner AP, Shaffer VO, Gangappa S, Keller SA, Bachmann MF et al. mTOR regulates memory CD8 T-cell differentiation. Nature 2009; 460: 108–112.

    CAS  PubMed  PubMed Central  Google Scholar 

  151. Rao RR, Li Q, Odunsi K, Shrikant PA . The mTOR kinase determines effector versus memory CD8+ T cell fate by regulating the expression of transcription factors T-bet and Eomesodermin. Immunity 2010; 32: 67–78.

    PubMed  PubMed Central  Google Scholar 

  152. Li Q, Rao RR, Araki K, Pollizzi K, Odunsi K, Powell JD et al. A central role for mTOR kinase in homeostatic proliferation induced CD8+ T cell memory and tumor immunity. Immunity 2011; 34: 541–553.

    CAS  PubMed  PubMed Central  Google Scholar 

  153. Liu G, Yang K, Burns S, Shrestha S, Chi H . The S1P1–mTOR axis directs the reciprocal differentiation of TH1 and Treg cells. Nat Immunol 2010; 11: 1047–1056.

    CAS  PubMed  PubMed Central  Google Scholar 

  154. Lee K, Gudapati P, Dragovic S, Spencer C, Joyce S, Killeen N et al. Mammalian target of rapamycin protein complex 2 regulates differentiation of Th1 and Th2 cell subsets via distinct signaling pathways. Immunity 2010; 32: 743–753.

    CAS  PubMed  PubMed Central  Google Scholar 

  155. Powell JD, Delgoffe GM . The mammalian target of rapamycin: linking T cell differentiation, function, and metabolism. Immunity 2010; 33: 301–311.

    CAS  PubMed  PubMed Central  Google Scholar 

  156. Delgoffe GM, Kole TP, Zheng Y, Zarek PE, Matthews KL, Xiao B et al. The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment. Immunity 2009; 30: 832–844.

    CAS  PubMed  PubMed Central  Google Scholar 

  157. Delgoffe GM, Pollizzi KN, Waickman AT, Heikamp E, Meyers DJ, Horton MR et al. The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2. Nat Immunol 2011; 12: 295–303.

    CAS  PubMed  PubMed Central  Google Scholar 

  158. Michalek RD, Gerriets VA, Jacobs SR, Macintyre AN, MacIver NJ, Mason EF et al. Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J Immunol 2011; 186: 3299–3303.

    CAS  PubMed  Google Scholar 

  159. O'Connell RM, Rao DS, Chaudhuri AA, Baltimore D . Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol 2010; 10: 111–122.

    CAS  PubMed  Google Scholar 

  160. O'Connell RM, Taganov KD, Boldin MP, Cheng G, Baltimore D . MicroRNA-155 is induced during the macrophage inflammatory response. Proc Natl Acad Sci USA 2007; 104: 1604–1609.

    CAS  PubMed  PubMed Central  Google Scholar 

  161. Bezman NA, Cedars E, Steiner DF, Blelloch R, Hesslein DG, Lanier LL . Distinct requirements of microRNAs in NK cell activation, survival, and function. J Immunol 2010; 185: 3835–3846.

    CAS  PubMed  Google Scholar 

  162. Taganov KD, Boldin MP, Chang KJ, Baltimore D . NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci USA 2006; 103: 12481–12486.

    CAS  PubMed  PubMed Central  Google Scholar 

  163. Li QJ, Chau J, Ebert PJ, Sylvester G, Min H, Liu G et al. miR-181a is an intrinsic modulator of T cell sensitivity and selection. Cell 2007; 129: 147–161.

    CAS  PubMed  Google Scholar 

  164. Ebert PJ, Jiang S, Xie J, Li QJ, Davis MM . An endogenous positively selecting peptide enhances mature T cell responses and becomes an autoantigen in the absence of microRNA miR-181a. Nat Immunol 2009; 10: 1162–1169.

    CAS  PubMed  PubMed Central  Google Scholar 

  165. Stittrich AB, Haftmann C, Sgouroudis E, Kühl AA, Hegazy AN, Panse I et al. The microRNA miR-182 is induced by IL-2 and promotes clonal expansion of activated helper T lymphocytes. Nat Immunol 2010; 11: 1057–1062.

    CAS  PubMed  Google Scholar 

  166. Lu LF, Boldin MP, Chaudhry A, Lin LL, Taganov KD, Hanada T et al. Function of miR-146a in controlling Treg cells cell-mediated regulation of Th1 responses. Cell 2010; 142: 914–929.

    CAS  PubMed  PubMed Central  Google Scholar 

  167. O'Connell RM, Kahn D, Gibson WS, Round JL, Scholz RL, Chaudhuri AA et al. MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T cell development. Immunity 2010; 33: 607–619.

    CAS  PubMed  PubMed Central  Google Scholar 

  168. Du C, Liu C, Kang J, Zhao G, Ye Z, Huang S et al. MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis. Nat Immunol 2009; 10: 1252–1259.

    CAS  PubMed  Google Scholar 

  169. Leavy O . Immune regulation: (micro)Control of IFNγ. Nat Rev Immunol 2011; 11: 573.

    CAS  PubMed  Google Scholar 

  170. Ma F, Xu S, Liu X, Zhang Q, Xu X, Liu M et al. The microRNA miR-29 controls innate and adaptive immune responses to intracellular bacterial infection by targeting interferon-γ. Nat Immunol 2011; 12: 861–869.

    CAS  PubMed  Google Scholar 

  171. Steiner DF, Thomas MF, Hu JK, Yang Z, Babiarz JE, Allen CD et al. MicroRNA-29 regulates T-box transcription factors and interferon-γ production in helper T cells. Immunity 2011; 35: 169–181.

    CAS  PubMed  PubMed Central  Google Scholar 

  172. Rossi RL, Rossetti G, Wenandy L, Curti S, Ripamonti A, Bonnal RJ et al. Distinct microRNA signatures in human lymphocyte subsets and enforcement of the naive state in CD4+ T cells by the microRNA miR-125b. Nat Immunol 2011; 12: 796–803.

    CAS  PubMed  Google Scholar 

  173. Oertli M, Engler DB, Kohler E, Koch M, Meyer TF, Müller A . MicroRNA-155 is essential for the T cell-mediated control of helicobacter pylori infection and for the induction of chronic gastritis and colitis. J Immunol 2011; 187: 3578–3586.

    CAS  PubMed  Google Scholar 

  174. Blüml S, Bonelli M, Niederreiter B, Puchner A, Mayr G, Hayer S et al. Essential role of microRNA-155 in the pathogenesis of autoimmune arthritis in mice. Arthritis Rheum 2011; 63: 1281–1288.

    PubMed  Google Scholar 

  175. Baltimore D, Boldin MP, O'Connell RM, Rao DS, Taganov KD . MicroRNAs: new regulators of immune cell development and function. Nat Immunol 2008; 9: 839–845.

    CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Dr J Liu, National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China. E-mail: liujuan.0405@163.com

  2. Dr XT Cao, National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai 200433, China. E-mail: caoxt@immunol.org

Authors and Affiliations

  1. National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, Shanghai, China

    Juan Liu, Shuxun Liu & Xuetao Cao

  2. National Key Laboratory of Medical Molecular Biology and Department of Immunology, Chinese Academy of Medical Sciences, Beijing, China

    Xuetao Cao

Authors
  1. Juan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shuxun Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xuetao Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, J., Liu, S. & Cao, X. Highlights of the advances in basic immunology in 2011. Cell Mol Immunol 9, 197–207 (2012). https://doi.org/10.1038/cmi.2012.12

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/cmi.2012.12

Keywords

This article is cited by

Search

Advanced search

Quick links