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.

  • Opinion
  • Published:

Antiviral TRIMs: friend or foe in autoimmune and autoinflammatory disease?

Nature Reviews Immunology volume 11, pages 617–625 (2011)Cite this article

Subjects

Abstract

The concept that viral sensing systems, via their ability to drive pro-inflammatory cytokine and interferon production, contribute to the development of autoimmune and autoinflammatory disease is supported by a wide range of clinical and experimental observations. Recently, the tripartite motif-containing proteins (TRIMs) have emerged as having key roles in antiviral immunity — either as viral restriction factors or as regulators of pathways downstream of viral RNA and DNA sensors, and the inflammasome. Given their involvement in these pathways, we propose that TRIM proteins contribute to the development and pathology of autoimmune and autoinflammatory conditions, thus making them potential novel targets for therapeutic manipulation.

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

Figure 1: TRIM-mediated regulation of TLR and RLR pathways.
Figure 2: TRIM-mediated regulation of NLRP1 and NLRP3 inflammasome pathways.

Similar content being viewed by others

References

  1. Ozato, K., Shin, D. M., Chang, T. H. & Morse, H. C. TRIM family proteins and their emerging roles in innate immunity. Nature Rev. Immunol. 8, 849–860 (2008).

    CAS  Google Scholar 

  2. Stremlau, M. et al. The cytoplasmic body component TRIM5α restricts HIV-1 infection in Old World monkeys. Nature 427, 848–853 (2004).

    CAS  PubMed  Google Scholar 

  3. Gao, B., Duan, Z., Xu, W. & Xiong, S. Tripartite motif-containing 22 inhibits the activity of hepatitis B virus core promoter, which is dependent on nuclear-located RING domain. Hepatology 50, 424–433 (2009).

    CAS  PubMed  Google Scholar 

  4. Rowe, H. M. et al. KAP1 controls endogenous retroviruses in embryonic stem cells. Nature 463, 237–240 (2010).

    CAS  PubMed  Google Scholar 

  5. McNab, F. W., Rajsbaum, R., Stoye, J. P. & O'Garra, A. Tripartite-motif proteins and innate immune regulation. Curr. Opin. Immunol. 23, 46–56 (2011).

    CAS  PubMed  Google Scholar 

  6. Koffler, D., Carr, R., Agnello, V., Thoburn, R. & Kunkel, H. G. Antibodies to polynucleotides in human sera: antigenic specificity and relation to disease. J. Exp. Med. 134, 294–312 (1971).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Martinon, F., Petrilli, V., Mayor, A., Tardivel, A. & Tschopp, J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440, 237–241 (2006).

    CAS  PubMed  Google Scholar 

  8. Masters, S. L. et al. Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1β in type 2 diabetes. Nature Immunol. 11, 897–904 (2010).

    CAS  Google Scholar 

  9. Rehaume, L. M., Jouault, T. & Chamaillard, M. Lessons from the inflammasome: a molecular sentry linking Candida and Crohn's disease. Trends Immunol. 31, 171–175 (2010).

    CAS  PubMed  Google Scholar 

  10. Schroder, K., Zhou, R. & Tschopp, J. The NLRP3 inflammasome: a sensor for metabolic danger? Science 327, 296–300 (2010).

    CAS  PubMed  Google Scholar 

  11. Banchereau, J. & Pascual, V. Type I interferon in systemic lupus erythematosus and other autoimmune diseases. Immunity 25, 383–392 (2006).

    CAS  PubMed  Google Scholar 

  12. Gilliet, M., Cao, W. & Liu, Y. J. Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases. Nature Rev. Immunol. 8, 594–606 (2008).

    CAS  Google Scholar 

  13. Kyogoku, C. & Tsuchiya, N. A compass that points to lupus: genetic studies on type I interferon pathway. Genes Immun. 8, 445–455 (2007).

    CAS  PubMed  Google Scholar 

  14. Barbalat, R., Ewald, S. E., Mouchess, M. L. & Barton, G. M. Nucleic acid recognition by the innate immune system. Annu. Rev. Immunol. 29, 185–214 (2011).

    CAS  PubMed  Google Scholar 

  15. Lau, C. M. et al. RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement. J. Exp. Med. 202, 1171–1177 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Leadbetter, E. A. et al. Chromatin–IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors. Nature 416, 603–607 (2002).

    CAS  PubMed  Google Scholar 

  17. Laragione, T., Brenner, M., Li, W. & Gulko, P. S. Cia5d regulates a new fibroblast-like synoviocyte invasion-associated gene expression signature. Arthritis Res. Ther. 10, R92 (2008).

    PubMed  PubMed Central  Google Scholar 

  18. Oke, V. et al. High Ro52 expression in spontaneous and UV-induced cutaneous inflammation. J. Invest. Dermatol. 129, 2000–2010 (2009).

    CAS  PubMed  Google Scholar 

  19. Carthagena, L. et al. Human TRIM gene expression in response to interferons. PLoS ONE 4, e4894 (2009).

    PubMed  PubMed Central  Google Scholar 

  20. Rajsbaum, R., Stoye, J. P. & O'Garra, A. Type I interferon-dependent and -independent expression of tripartite motif proteins in immune cells. Eur. J. Immunol. 38, 619–630 (2008).

    CAS  PubMed  Google Scholar 

  21. Scofield, R. H., Farris, A. D., Horsfall, A. C. & Harley, J. B. Fine specificity of the autoimmune response to the Ro/SSA and La/SSB ribonucleoproteins. Arthritis Rheum. 42, 199–209 (1999).

    CAS  PubMed  Google Scholar 

  22. Kong, H. J. et al. Cutting edge: autoantigen Ro52 is an interferon inducible E3 ligase that ubiquitinates IRF-8 and enhances cytokine expression in macrophages. J. Immunol. 179, 26–30 (2007).

    CAS  PubMed  Google Scholar 

  23. Higgs, R. et al. The E3 ubiquitin ligase Ro52 negatively regulates IFN-β production post-pathogen recognition by polyubiquitin-mediated degradation of IRF3. J. Immunol. 181, 1780–1786 (2008).

    CAS  PubMed  Google Scholar 

  24. Yang, K. et al. TRIM21 is essential to sustain IFN regulatory factor 3 activation during antiviral response. J. Immunol. 182, 3782–3792 (2009).

    CAS  PubMed  Google Scholar 

  25. Young, J. A. et al. Fas-associated death domain (FADD) and the E3 ubiquitin-protein ligase TRIM21 interact to negatively regulate virus-induced interferon production. J. Biol. Chem. 286, 6521–6531 (2011).

    CAS  PubMed  Google Scholar 

  26. Espinosa, A. et al. Loss of the lupus autoantigen Ro52/Trim21 induces tissue inflammation and systemic autoimmunity by disregulating the IL-23–Th17 pathway. J. Exp. Med. 206, 1661–1671 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Yoshimi, R. et al. Gene disruption study reveals a nonredundant role for TRIM21/Ro52 in NF-κB-dependent cytokine expression in fibroblasts. J. Immunol. 182, 7527–7538 (2009).

    CAS  PubMed  Google Scholar 

  28. Higgs, R. et al. Self protection from anti-viral responses — Ro52 promotes degradation of the transcription factor IRF7 downstream of the viral Toll-like receptors. PLoS ONE 5, e11776 (2010).

    PubMed  PubMed Central  Google Scholar 

  29. Ozato, K. et al. Comment on “Gene disruption study reveals a nonredundant role for TRIM21/Ro52 in NF-κB-dependent cytokine expression in fibroblasts”. J. Immunol. 183, 7619 (2009).

    CAS  PubMed  Google Scholar 

  30. Espinosa, A., Brauner, S., Ambrosi, A., Kuchroo, V. K. & Wahren-Herlenius, M. Response to comment on “Gene disruption study reveals a nonredundant role for TRIM21/Ro52 in NF-κB-dependent cytokine expression in fibroblasts”. J. Immunol. 183, 7620–7621 (2009).

    CAS  Google Scholar 

  31. Mallery, D. L. et al. Antibodies mediate intracellular immunity through tripartite motif-containing 21 (TRIM21). Proc. Natl Acad. Sci. USA 107, 19985–19990 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Beer, H. D. et al. The estrogen-responsive B box protein: a novel regulator of keratinocyte differentiation. J. Biol. Chem. 277, 20740–20749 (2002).

    CAS  PubMed  Google Scholar 

  33. Cheung, B. B. et al. The estrogen-responsive B box protein is a novel regulator of the retinoid signal. J. Biol. Chem. 281, 18246–18256 (2006).

    CAS  PubMed  Google Scholar 

  34. Marshall, G. M. et al. TRIM16 acts as a tumour suppressor by inhibitory effects on cytoplasmic vimentin and nuclear E2F1 in neuroblastoma cells. Oncogene 29, 6172–6183 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Vossenaar, E. R. et al. Rheumatoid arthritis specific anti-Sa antibodies target citrullinated vimentin. Arthritis Res. Ther. 6, R142–R150 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Van Steendam, K., Tilleman, K. & Deforce, D. The relevance of citrullinated vimentin in the production of antibodies against citrullinated proteins and the pathogenesis of rheumatoid arthritis. Rheumatology 50, 830–837 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Dejaco, C. et al. Diagnostic value of antibodies against a modified citrullinated vimentin in rheumatoid arthritis. Arthritis Res. Ther. 8, R119 (2006).

    PubMed  PubMed Central  Google Scholar 

  38. Mor-Vaknin, N., Punturieri, A., Sitwala, K. & Markovitz, D. M. Vimentin is secreted by activated macrophages. Nature Cell Biol. 5, 59–63 (2003).

    CAS  PubMed  Google Scholar 

  39. Kivity, S., Agmon-Levin, N., Blank, M. & Shoenfeld, Y. Infections and autoimmunity — friends or foes? Trends Immunol. 30, 409–414 (2009).

    CAS  PubMed  Google Scholar 

  40. Uchil, P. D., Quinlan, B. D., Chan, W. T., Luna, J. M. & Mothes, W. TRIM E3 ligases interfere with early and late stages of the retroviral life cycle. PLoS Pathog. 4, e16 (2008).

    PubMed  PubMed Central  Google Scholar 

  41. Balada, E., Vilardell-Tarres, M. & Ordi-Ros, J. Implication of human endogenous retroviruses in the development of autoimmune diseases. Int. Rev. Immunol. 29, 351–370 (2010).

    CAS  PubMed  Google Scholar 

  42. Baudino, L., Yoshinobu, K., Dunand-Sauthier, I., Evans, L. H. & Izui, S. TLR-mediated up-regulation of serum retroviral gp70 is controlled by the Sgp loci of lupus-prone mice. J. Autoimmun. 35, 153–159 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Baudino, L., Yoshinobu, K., Morito, N., Santiago-Raber, M. L. & Izui, S. Role of endogenous retroviruses in murine SLE. Autoimmun. Rev. 10, 27–34 (2010).

    CAS  PubMed  Google Scholar 

  44. Song, B. TRIM5α. Curr. Top. Microbiol. Immunol. 339, 47–66 (2009).

    CAS  PubMed  Google Scholar 

  45. Sebastian, S. & Luban, J. TRIM5α selectively binds a restriction-sensitive retroviral capsid. Retrovirology 2, 40 (2005).

    PubMed  PubMed Central  Google Scholar 

  46. Nexo, B. A. et al. The etiology of multiple sclerosis: genetic evidence for the involvement of the human endogenous retrovirus HERV-Fc1. PLoS ONE 6, e16652 (2011).

    PubMed  PubMed Central  Google Scholar 

  47. Wolf, D. & Goff, S. P. TRIM28 mediates primer binding site-targeted silencing of murine leukemia virus in embryonic cells. Cell 131, 46–57 (2007).

    CAS  PubMed  Google Scholar 

  48. Wolf, D. & Goff, S. P. Embryonic stem cells use ZFP809 to silence retroviral DNAs. Nature 458, 1201–1204 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Gack, M. U. et al. TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. Nature 446, 916–920 (2007).

    CAS  PubMed  Google Scholar 

  50. Zeng, W. et al. Reconstitution of the RIG-I pathway reveals a signaling role of unanchored polyubiquitin chains in innate immunity. Cell 141, 315–330 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Wang, P. et al. Caspase-12 controls West Nile virus infection via the viral RNA receptor RIG-I. Nature Immunol. 11, 912–919 (2010).

    CAS  Google Scholar 

  52. Tsuchida, T. et al. The ubiquitin ligase TRIM56 regulates innate immune responses to intracellular double-stranded DNA. Immunity 33, 765–776 (2010).

    CAS  PubMed  Google Scholar 

  53. Zha, J. et al. The Ret finger protein inhibits signaling mediated by the noncanonical and canonical IκB kinase family members. J. Immunol. 176, 1072–1080 (2006).

    CAS  PubMed  Google Scholar 

  54. Baranzini, S. E. The genetics of autoimmune diseases: a networked perspective. Curr. Opin. Immunol. 21, 596–605 (2009).

    CAS  PubMed  Google Scholar 

  55. Noguchi, K. et al. TRIM40 promotes neddylation of IKKγ and is downregulated in gastrointestinal cancers. Carcinogenesis 32, 995–1004 (2011).

    CAS  PubMed  Google Scholar 

  56. Arimoto, K. et al. Polyubiquitin conjugation to NEMO by triparite motif protein 23 (TRIM23) is critical in antiviral defense. Proc. Natl Acad. Sci. USA 107, 15856–15861 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Poole, E. et al. Identification of TRIM23 as a cofactor involved in the regulation of NF-κB by human cytomegalovirus. J. Virol. 83, 3581–3590 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Nishibori, T., Tanabe, Y., Su, L. & David, M. Impaired development of CD4+ CD25+ regulatory T cells in the absence of STAT1: increased susceptibility to autoimmune disease. J. Exp. Med. 199, 25–34 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Bettelli, E. et al. Loss of T-bet, but not STAT1, prevents the development of experimental autoimmune encephalomyelitis. J. Exp. Med. 200, 79–87 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Sigurdsson, S. et al. Polymorphisms in the tyrosine kinase 2 and interferon regulatory factor 5 genes are associated with systemic lupus erythematosus. Am. J. Hum. Genet. 76, 528–537 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Graham, R. R. et al. A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus. Nature Genet. 38, 550–555 (2006).

    CAS  PubMed  Google Scholar 

  62. Salloum, R. et al. Genetic variation at the IRF7/PHRF1 locus is associated with autoantibody profile and serum interferon-α activity in lupus patients. Arthritis Rheum. 62, 553–561 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Feng, D. et al. Genetic variants and disease-associated factors contribute to enhanced interferon regulatory factor 5 expression in blood cells of patients with systemic lupus erythematosus. Arthritis Rheum. 62, 562–573 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Kamitani, S. et al. KAP1 regulates type I interferon/STAT1-mediated IRF-1 gene expression. Biochem. Biophys. Res. Commun. 370, 366–370 (2008).

    CAS  PubMed  Google Scholar 

  65. Tsuruma, R. et al. Physical and functional interactions between STAT3 and KAP1. Oncogene 27, 3054–3059 (2008).

    CAS  PubMed  Google Scholar 

  66. Wada, K., Niida, M., Tanaka, M. & Kamitani, T. Ro52-mediated monoubiquitination of IKKβ down-regulates NF-κB signalling. J. Biochem. 146, 821–832 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Niida, M., Tanaka, M. & Kamitani, T. Downregulation of active IKKβ by Ro52-mediated autophagy. Mol. Immunol. 47, 2378–2387 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Everett, R. D. & Chelbi-Alix, M. K. PML and PML nuclear bodies: implications in antiviral defence. Biochimie 89, 819–830 (2007).

    CAS  PubMed  Google Scholar 

  69. El Bougrini, J., Dianoux, L. & Chelbi-Alix, M. K. PML positively regulates interferon γ signaling. Biochimie 93, 389–398 (2011).

    CAS  PubMed  Google Scholar 

  70. Wu, W. S., Xu, Z. X. & Chang, K. S. The promyelocytic leukemia protein represses A20-mediated transcription. J. Biol. Chem. 277, 31734–31739 (2002).

    CAS  PubMed  Google Scholar 

  71. Wu, W. S. et al. Promyelocytic leukemia protein sensitizes tumor necrosis factor α-induced apoptosis by inhibiting the NF-κB survival pathway. J. Biol. Chem. 278, 12294–12304 (2003).

    CAS  PubMed  Google Scholar 

  72. Xu, D. et al. Promyelocytic leukemia zinc finger protein regulates interferon-mediated innate immunity. Immunity 30, 802–816 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Stinton, L. M., Swain, M., Myers, R. P., Shaheen, A. A. & Fritzler, M. J. Autoantibodies to GW bodies and other autoantigens in primary biliary cirrhosis. Clin. Exp. Immunol. 163, 147–156 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Fracchia, M. et al. Serum interferon γ in primary biliary cirrhosis: effect of ursodeoxycholic acid and prednisone therapy alone and in combination. Eur. J. Gastroenterol. Hepatol. 12, 463–468 (2000).

    CAS  PubMed  Google Scholar 

  75. Okumura, F., Matsunaga, Y., Katayama, Y., Nakayama, K. I. & Hatakeyama, S. TRIM8 modulates STAT3 activity through negative regulation of PIAS3. J. Cell Sci. 123, 2238–2245 (2010).

    CAS  PubMed  Google Scholar 

  76. Okumura, F., Okumura, A. J., Matsumoto, M., Nakayama, K. I. & Hatakeyama, S. TRIM8 regulates Nanog via Hsp90β-medicated nuclear translocation of STAT3 in embryonic stem cells. Biochim. Biophys. Acta 2 Jun 2011 (doi:10.1016/j.bbamcr.2011.05.013).

    CAS  Google Scholar 

  77. Ben-Zvi, I. & Livneh, A. Chronic inflammation in FMF: markers, risk factors, outcomes and therapy. Nature Rev. Rheumatol. 7, 105–112 (2011).

    CAS  Google Scholar 

  78. Shaw, P. J., McDermott, M. F. & Kanneganti, T. D. Inflammasomes and autoimmunity. Trends Mol. Med. 17, 57–64 (2011).

    CAS  PubMed  Google Scholar 

  79. Richards, N. et al. Interaction between pyrin and the apoptotic speck protein (ASC) modulates ASC-induced apoptosis. J. Biol. Chem. 276, 39320–39329 (2001).

    CAS  PubMed  Google Scholar 

  80. Yu, J. W. et al. Pyrin activates the ASC pyroptosome in response to engagement by autoinflammatory PSTPIP1 mutants. Mol. Cell 28, 214–227 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Papin, S. et al. The SPRY domain of Pyrin, mutated in familial Mediterranean fever patients, interacts with inflammasome components and inhibits proIL-1β processing. Cell Death Differ. 14, 1457–1466 (2007).

    CAS  PubMed  Google Scholar 

  82. Yu, J. W. et al. Cryopyrin and pyrin activate caspase-1, but not NF-κB, via ASC oligomerization. Cell Death Differ. 13, 236–249 (2006).

    CAS  PubMed  Google Scholar 

  83. Chae, J. J. et al. The familial Mediterranean fever protein, pyrin, is cleaved by caspase-1 and activates NF-κB through its N-terminal fragment. Blood 112, 1794–1803 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Chae, J. J. et al. The B30.2 domain of pyrin, the familial Mediterranean fever protein, interacts directly with caspase-1 to modulate IL-1β production. Proc. Natl Acad. Sci. USA 103, 9982–9987 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Unal, A., Dursun, A., Emre, U., Tascilar, N. F. & Ankarali, H. Evaluation of common mutations in the Mediterranean fever gene in multiple sclerosis patients: is it a susceptibility gene? J. Neurol. Sci. 294, 38–42 (2010).

    CAS  PubMed  Google Scholar 

  86. Yahalom, G. et al. Familial Mediterranean fever (FMF) and multiple sclerosis: an association study in one of the world's largest FMF cohorts. Eur. J. Neurol. 8 Feb 2011 (doi:10.1111/j.1468-1331.2011.0 3356.x).

  87. Merrill, J. E. Proinflammatory and antiinflammatory cytokines in multiple sclerosis and central nervous system acquired immunodeficiency syndrome. J. Immunother. 12, 167–170 (1992).

    CAS  PubMed  Google Scholar 

  88. Shoham, N. G. et al. Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean fever and PAPA syndrome as disorders in the same pathway. Proc. Natl Acad. Sci. USA 100, 13501–13506 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Munding, C. et al. The estrogen-responsive B box protein: a novel enhancer of interleukin-1β secretion. Cell Death Differ. 13, 1938–1949 (2006).

    CAS  PubMed  Google Scholar 

  90. Hu, Y. et al. Tripartite-motif protein 30 negatively regulates NLRP3 inflammasome activation by modulating reactive oxygen species production. J. Immunol. 185, 7699–7705 (2010).

    CAS  PubMed  Google Scholar 

  91. Zhou, R., Yazdi, A. S., Menu, P. & Tschopp, J. A role for mitochondria in NLRP3 inflammasome activation. Nature 469, 221–225 (2011).

    CAS  PubMed  Google Scholar 

  92. Shi, M. et al. TRIM30α negatively regulates TLR-mediated NF-κB activation by targeting TAB2 and TAB3 for degradation. Nature Immunol. 9, 369–377 (2008).

    CAS  Google Scholar 

  93. Tareen, S. U. & Emerman, M. Human Trim5α has additional activities that are uncoupled from retroviral capsid recognition. Virology 409, 113–120 (2011).

    CAS  PubMed  Google Scholar 

  94. Pertel, T. et al. TRIM5 is an innate immune sensor for the retrovirus capsid lattice. Nature 472, 361–365 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Reymond, A. et al. The tripartite motif family identifies cell compartments. EMBO J. 20, 2140–2151 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Asaoka, K. et al. A retrovirus restriction factor TRIM5α is transcriptionally regulated by interferons. Biochem. Biophys. Res. Commun. 338, 1950–1956 (2005).

    CAS  PubMed  Google Scholar 

  97. Chelbi-Alix, M. K. et al. Induction of the PML protein by interferons in normal and APL cells. Leukemia 9, 2027–2033 (1995).

    CAS  PubMed  Google Scholar 

  98. Strandberg, L. et al. Interferon-α induces up-regulation and nuclear translocation of the Ro52 autoantigen as detected by a panel of novel Ro52-specific monoclonal antibodies. J. Clin. Immunol. 28, 220–231 (2008).

    CAS  PubMed  Google Scholar 

  99. Casciola-Rosen, L. A., Anhalt, G. & Rosen, A. Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes. J. Exp. Med. 179, 1317–1330 (1994).

    CAS  PubMed  Google Scholar 

  100. Ohlsson, M., Jonsson, R. & Brokstad, K. A. Subcellular redistribution and surface exposure of the Ro52, Ro60 and La48 autoantigens during apoptosis in human ductal epithelial cells: a possible mechanism in the pathogenesis of Sjogren's syndrome. Scand. J. Immunol. 56, 456–469 (2002).

    CAS  PubMed  Google Scholar 

  101. Chae, J. J. et al. Targeted disruption of pyrin, the FMF protein, causes heightened sensitivity to endotoxin and a defect in macrophage apoptosis. Mol. Cell 11, 591–604 (2003).

    CAS  PubMed  Google Scholar 

  102. Hoshino, K. et al. Anti-MDA5 and anti-TIF1-γ antibodies have clinical significance for patients with dermatomyositis. Rheumatology 49, 726–1733 (2010).

    Google Scholar 

  103. Randrianarison-Huetz, V. et al. Gfi-1B controls human erythroid and megakaryocytic differentiation by regulating TGF-β signaling at the bipotent erythro-megakaryocytic progenitor stage. Blood 115, 2784–2795 (2010).

    CAS  PubMed  Google Scholar 

  104. Billaut-Mulot, O. et al. SS-56, a novel cellular target of autoantibody responses in Sjogren syndrome and systemic lupus erythematosus. J. Clin. Invest. 108, 861–869 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge Science Foundation Ireland (grants 05/PICA/B815 and 08/IN.1/B2091) and the Health Research Board, Ireland (grant PHD/2007/11) for financial support associated with this work.

Author information

Authors and Affiliations

  1. Caroline Jefferies and Claire Wynne are at Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland.,

    Caroline Jefferies & Claire Wynne

  2. Rowan Higgs is at the Immunology Research Centre, School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland.,

    Rowan Higgs

Authors
  1. Caroline Jefferies
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Claire Wynne
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rowan Higgs
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Caroline Jefferies.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Figure 1

TRIM structure and genomic clusters. (PDF 253 kb)

Supplementary Figure 2

TRIM family and domain structures. (PDF 323 kb)

Related links

Related links

FURTHER INFORMATION

Caroline Jefferies's homepage

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jefferies, C., Wynne, C. & Higgs, R. Antiviral TRIMs: friend or foe in autoimmune and autoinflammatory disease?. Nat Rev Immunol 11, 617–625 (2011). https://doi.org/10.1038/nri3043

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nri3043

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing