Latest Research

  • Article |

    lncRNAs can regulate immune responses at a number of levels. Song and colleagues demonstrate that the lncRNA NKILA is expressed by tumor-associated cytotoxic T cells, and this predisposes them to activation-induced cell death and escape of tumors from immunologically mediated destruction.

    • Di Huang
    • , Jianing Chen
    • , Linbin Yang
    • , Qian Ouyang
    • , Jiaqian Li
    • , Liyan Lao
    • , Jinghua Zhao
    • , Jiang Liu
    • , Yiwen Lu
    • , Yue Xing
    • , Fei Chen
    • , Fengxi Su
    • , Herui Yao
    • , Qiang Liu
    • , Shicheng Su
    •  & Erwei Song
  • Article |

    Polić and colleagues show that the activating receptor NKG2D specifically sets the activation threshold for the activating receptor NCR1, providing a mechanism distinct from previously known mechanisms of NK cell education.

    • Vedrana Jelenčić
    • , Marko Šestan
    • , Inga Kavazović
    • , Maja Lenartić
    • , Sonja Marinović
    • , Tim D. Holmes
    • , Michaela Prchal-Murphy
    • , Berislav Lisnić
    • , Veronika Sexl
    • , Yenan T. Bryceson
    • , Felix M. Wensveen
    •  & Bojan Polić
  • Article |

    TH17 cells contribute to anti-fungal and anti-bacterial adaptive immune responses. Sallusto and colleagues show that the transcription factor c-Maf has an immunoregulatory role in directing gene expression and tissue residency in human IL-10+ TH17 cell subsets.

    • Dominik Aschenbrenner
    • , Mathilde Foglierini
    • , David Jarrossay
    • , Dan Hu
    • , Howard L. Weiner
    • , Vijay K. Kuchroo
    • , Antonio Lanzavecchia
    • , Samuele Notarbartolo
    •  & Federica Sallusto
  • Article |

    The receptor TLR3 is essential for effective responses to herpes simplex virus type 1. Miyake and colleagues demonstrate that a neuron- and astrocyte-intrinsic pathway of TLR3 and the metabolic checkpoint kinase complex mTORC2 is needed to prevent fulminant infection with this virus and encephalitis.

    • Ryota Sato
    • , Akihisa Kato
    • , Takahiko Chimura
    • , Shin-Ichiroh Saitoh
    • , Takuma Shibata
    • , Yusuke Murakami
    • , Ryutaro Fukui
    • , Kaiwen Liu
    • , Yun Zhang
    • , Jun Arii
    • , Ge-Hong Sun-Wada
    • , Yoh Wada
    • , Tsuneo Ikenoue
    • , Glen N. Barber
    • , Toshiya Manabe
    • , Yasushi Kawaguchi
    •  & Kensuke Miyake
  • Article |

    Locksley et al. show tissue-specific imprinting dictates the activating receptors ILC2s express, even in germ-free mice. Skin ILC2s are preferentially activated by IL-18, and IL-18 contributes to inflammation in a mouse model of atopic dermatitis.

    • Roberto R. Ricardo-Gonzalez
    • , Steven J. Van Dyken
    • , Christoph Schneider
    • , Jinwoo Lee
    • , Jesse C. Nussbaum
    • , Hong-Erh Liang
    • , Dedeepya Vaka
    • , Walter L. Eckalbar
    • , Ari B. Molofsky
    • , David J. Erle
    •  & Richard M. Locksley
  • Review Article |

    He and Wang review the immunological functions of RIP kinases in inflammatory responses to microbial infection and tissue injury, as well as their potential roles in the pathogenesis of inflammatory disease and aging.

    • Sudan He
    •  & Xiaodong Wang
  • Article |

    Patients who express a hyperactive mutant of the kinase PI3K exhibit defective humoral immunity. Preite et al. show that overactive PI3K leads to defective class-switched antigen-specific responses to immunization, despite augmented germinal-center formation and reactivity to commensal microbes and self antigens.

    • Silvia Preite
    • , Jennifer L. Cannons
    • , Andrea J. Radtke
    • , Ivan Vujkovic-Cvijin
    • , Julio Gomez-Rodriguez
    • , Stefano Volpi
    • , Bonnie Huang
    • , Jun Cheng
    • , Nicholas Collins
    • , Julie Reilley
    • , Robin Handon
    • , Kerry Dobbs
    • , Lutfi Huq
    • , Indu Raman
    • , Chengsong Zhu
    • , Quan-Zhen Li
    • , Ming O. Li
    • , Stefania Pittaluga
    • , Gulbu Uzel
    • , Luigi D. Notarangelo
    • , Yasmine Belkaid
    • , Ronald N. Germain
    •  & Pamela L. Schwartzberg
  • Article |

    Primary immunodeficiency can predispose patients to mycobacterial disease. Casanova and colleagues identify novel human mutations in the enzyme SPPL2A that result in selective accumulation of CD74 in a dendritic cell subset and lead to their death and the failure to mount effective TH1 responses.

    • Xiao-Fei Kong
    • , Ruben Martinez-Barricarte
    • , James Kennedy
    • , Federico Mele
    • , Tomi Lazarov
    • , Elissa K. Deenick
    • , Cindy S. Ma
    • , Gaëlle Breton
    • , Kimberly B. Lucero
    • , David Langlais
    • , Aziz Bousfiha
    • , Caner Aytekin
    • , Janet Markle
    • , Céline Trouillet
    • , Fabienne Jabot-Hanin
    • , Cecilia S. Lindestam Arlehamn
    • , Geetha Rao
    • , Capucine Picard
    • , Théo Lasseau
    • , Daniela Latorre
    • , Sophie Hambleton
    • , Caroline Deswarte
    • , Yuval Itan
    • , Katia Abarca
    • , Dewton Moraes-Vasconcelos
    • , Fatima Ailal
    • , Aydan Ikinciogullari
    • , Figen Dogu
    • , Ibtihal Benhsaien
    • , Alessandro Sette
    • , Laurent Abel
    • , Stéphanie Boisson-Dupuis
    • , Bernd Schröder
    • , Michel C. Nussenzweig
    • , Kang Liu
    • , Frédéric Geissmann
    • , Stuart G. Tangye
    • , Philippe Gros
    • , Federica Sallusto
    • , Jacinta Bustamante
    •  & Jean-Laurent Casanova
  • Article |

    Cohesin is a chromatin-binding factor that interacts at CTCF motifs to organize chromatin looping domains. Merkenschlager and colleagues show that cohesin regulates the inducible expression of inflammatory genes in macrophages and HSPCs and in human AML.

    • Sergi Cuartero
    • , Felix D. Weiss
    • , Gopuraja Dharmalingam
    • , Ya Guo
    • , Elizabeth Ing-Simmons
    • , Silvia Masella
    • , Irene Robles-Rebollo
    • , Xiaolin Xiao
    • , Yi-Fang Wang
    • , Iros Barozzi
    • , Dounia Djeghloul
    • , Mariane T. Amano
    • , Henri Niskanen
    • , Enrico Petretto
    • , Robin D. Dowell
    • , Kikuë Tachibana
    • , Minna U. Kaikkonen
    • , Kim A. Nasmyth
    • , Boris Lenhard
    • , Gioacchino Natoli
    • , Amanda G. Fisher
    •  & Matthias Merkenschlager
  • Article |

    Circulating IgG3 increases in chronic HIV infection. Moir and colleagues describe a negative regulatory role of secreted IgG3 in response to chronic HIV infection through its action on nonconventional CD27 memory B cells.

    • Lela Kardava
    • , Haewon Sohn
    • , Christine Youn
    • , James W. Austin
    • , Wei Wang
    • , Clarisa M. Buckner
    • , J. Shawn Justement
    • , Valerie A. Melson
    • , Gwynne E. Roth
    • , Marissa A. Hand
    • , Kathleen R. Gittens
    • , Richard W. Kwan
    • , Michael C. Sneller
    • , Yuxing Li
    • , Tae-Wook Chun
    • , Peter D. Sun
    • , Susan K. Pierce
    •  & Susan Moir
  • Article |

    Nemazee and colleagues show that PLD3 and PLD4 are endolysosomal exonucleases that digest ingested nucleic acids and thereby prevent activation of endosomal TLRs. Mice that lack PLD3 and PLD4 develop autoinflammatory disease.

    • Amanda L. Gavin
    • , Deli Huang
    • , Christoph Huber
    • , Annica Mårtensson
    • , Virginie Tardif
    • , Patrick D. Skog
    • , Tanya R. Blane
    • , Therese C. Thinnes
    • , Kent Osborn
    • , Hayley S. Chong
    • , Farnaz Kargaran
    • , Phoebe Kimm
    • , Armen Zeitjian
    • , Rachel L. Sielski
    • , Megan Briggs
    • , Sebastian R. Schulz
    • , Alessandro Zarpellon
    • , Benjamin Cravatt
    • , Ee Shan Pang
    • , John Teijaro
    • , Juan Carlos de la Torre
    • , Meredith O’Keeffe
    • , Hubertus Hochrein
    • , Markus Damme
    • , Luc Teyton
    • , Brian R. Lawson
    •  & David Nemazee
  • Article |

    Human follicular lymphomas arise from germinal center B cells. Milpied and colleagues use single-cell transcriptomic analysis to show that follicular lymphoma cells lose synchronized gene-expression patterns that characterize normal germinal center B cells.

    • Pierre Milpied
    • , Iñaki Cervera-Marzal
    • , Marie-Laure Mollichella
    • , Bruno Tesson
    • , Gabriel Brisou
    • , Alexandra Traverse-Glehen
    • , Gilles Salles
    • , Lionel Spinelli
    •  & Bertrand Nadel
  • Review Article |

    The immunoproteasome and thymoproteasome are specialized proteasomes operating within the immune system. In this Review, Murata et al. recount the discovery of the immunoproteasome and thymoproteasome and delve into their function, context in evolution and relation to human disease.

    • Shigeo Murata
    • , Yousuke Takahama
    • , Masanori Kasahara
    •  & Keiji Tanaka
  • Article |

    Natural killer (NK) cells can acquire ‘memory’ signatures. Sun and colleagues examine the dynamic ATAC-seq and functional RNA-seq changes observed upon generation of NK cell memory and show distinct roles for transcription factors STAT1 and STAT4.

    • Colleen M. Lau
    • , Nicholas M. Adams
    • , Clair D. Geary
    • , Orr-El Weizman
    • , Moritz Rapp
    • , Yuri Pritykin
    • , Christina S. Leslie
    •  & Joseph C. Sun
  • Article |

    Signaling via the cytokine IL-9 receptor regulates humoral recall responses. Kitamura and colleagues report that IL-9 triggers memory B cells to proliferate and terminally differentiate into antibody-secreting cells rather than re-entering germinal centers.

    • Shogo Takatsuka
    • , Hiroyuki Yamada
    • , Kei Haniuda
    • , Hiroshi Saruwatari
    • , Marina Ichihashi
    • , Jean-Christophe Renauld
    •  & Daisuke Kitamura
  • Review Article |

    Romagnani and colleagues discuss the specific recognition of viral antigens and peptides by NK cells and its implications for the composition of the NK cell repertoire and the selection of viral variants.

    • Quirin Hammer
    • , Timo Rückert
    •  & Chiara Romagnani
  • Article |

    Lymphocytes interpret antigenic signals into a functional response. Richard et al. demonstrate that the overall qualitative response by CTLs is independent of TCR ligand strength; instead, ligands determine the rate and uniformity at which CTLs respond.

    • Arianne C. Richard
    • , Aaron T. L. Lun
    • , Winnie W. Y. Lau
    • , Berthold Göttgens
    • , John C. Marioni
    •  & Gillian M. Griffiths
  • Article |

    Evidence of protective and homeostatic roles for IgE is relatively limited. Strid and colleagues demonstrate that γδ T cells induce switching to IgE that provides protection against experimentally induced epithelial cancer.

    • Greg Crawford
    • , Mark David Hayes
    • , Rocio Castro Seoane
    • , Sophie Ward
    • , Tim Dalessandri
    • , Chester Lai
    • , Eugene Healy
    • , David Kipling
    • , Charlotte Proby
    • , Colin Moyes
    • , Kile Green
    • , Katie Best
    • , Muzlifah Haniffa
    • , Marina Botto
    • , Deborah Dunn-Walters
    •  & Jessica Strid
  • Resource |

    Soumelis and colleagues use RNA-based sequencing to define the transcriptional signatures of DC subsets and monocytes-macrophages in human primary breast cancer.

    • Paula Michea
    • , Floriane Noël
    • , Eve Zakine
    • , Urszula Czerwinska
    • , Philémon Sirven
    • , Omar Abouzid
    • , Christel Goudot
    • , Alix Scholer-Dahirel
    • , Anne Vincent-Salomon
    • , Fabien Reyal
    • , Sebastian Amigorena
    • , Maude Guillot-Delost
    • , Elodie Segura
    •  & Vassili Soumelis
  • Article |

    TCRs are often thought to be pre-clustered before T cell activation. Rossboth et al. use super-resolution microscopy and statistical image analysis to demonstrate that TCRs are in fact randomly distributed on resting T cells.

    • Benedikt Rossboth
    • , Andreas M. Arnold
    • , Haisen Ta
    • , René Platzer
    • , Florian Kellner
    • , Johannes B. Huppa
    • , Mario Brameshuber
    • , Florian Baumgart
    •  & Gerhard J. Schütz
  • Article |

    B cells need at least two signals to terminally differentiate into antibody-secreting cells. Pierce and colleagues show that persistent exposure to antigen in the absence of T cell help or ‘pathogen pattern motifs’ leads to B cell death via a calcium-dependent ‘metabolic timer’.

    • Munir Akkaya
    • , Javier Traba
    • , Alexander S. Roesler
    • , Pietro Miozzo
    • , Billur Akkaya
    • , Brandon P. Theall
    • , Haewon Sohn
    • , Mirna Pena
    • , Margery Smelkinson
    • , Juraj Kabat
    • , Eric Dahlstrom
    • , David W. Dorward
    • , Jeff Skinner
    • , Michael N. Sack
    •  & Susan K. Pierce
  • Article |

    Foxo proteins are required for maintaining T cell quiescence. Turka and colleagues use a constitutively active Foxo1 in Treg cells to show that its downregulation is essential for maintaining their fitness in a competitive environment.

    • Ryan H. Newton
    • , Sharad Shrestha
    • , Jenna M. Sullivan
    • , Kathleen B. Yates
    • , Ewoud B. Compeer
    • , Noga Ron-Harel
    • , Bruce R. Blazar
    • , Steven J. Bensinger
    • , W. Nicholas Haining
    • , Michael L. Dustin
    • , Daniel J. Campbell
    • , Hongbo Chi
    •  & Laurence A. Turka
  • Article |

    Wolkers and colleagues show that the RNA-binding protein ZFP36L2 represses the translation of pre-formed cytokine-encoding mRNAs in memory T cells.

    • Fiamma Salerno
    • , Sander Engels
    • , Maartje van den Biggelaar
    • , Floris P. J. van Alphen
    • , Aurelie Guislain
    • , Wanqi Zhao
    • , Deborah L. Hodge
    • , Sarah E. Bell
    • , Jan Paul Medema
    • , Marieke von Lindern
    • , Martin Turner
    • , Howard A. Young
    •  & Monika C. Wolkers
  • Article |

    Regulatory factor X (RFX) is a transcription factor family comprising seven known members, yet the functional roles of RFX7 remain unknown. Guarda and colleagues show that RFX7 regulates natural killer (NK) cell survival and activity by limiting their cellular metabolism.

    • Wilson Castro
    • , Sonia T. Chelbi
    • , Charlène Niogret
    • , Cristina Ramon-Barros
    • , Suzanne P. M. Welten
    • , Kevin Osterheld
    • , Haiping Wang
    • , Giorgia Rota
    • , Leonor Morgado
    • , Eric Vivier
    • , Miro E. Raeber
    • , Onur Boyman
    • , Mauro Delorenzi
    • , David Barras
    • , Ping-Chih Ho
    • , Annette Oxenius
    •  & Greta Guarda
  • Review Article |

    The thymus has a critical role in the establishment of appropriately educated and self-tolerant T cells. In their Focus Review, Cheng and Anderson discuss the most recent insights into how the thymus establishes self-tolerance.

    • Mickie Cheng
    •  & Mark S. Anderson
  • Review Article |

    Treg cells have a critical role in maintaining peripheral tolerance. In this Focus Review, Dominguez-Villar and Hafler describe how the instability and plasticity of Treg cells can contribute to the breakdown of tolerance and lead to autoimmune disease.

    • Margarita Dominguez-Villar
    •  & David A. Hafler
  • Review Article |

    The rates of autoimmune disease are rising more rapidly than can be explained by changes in genetics. In this Focus Review, Verdu and Danska describe the dietary and microbial influences on type 1 diabetes and draw comparisons with celiac disease.

    • Elena F. Verdu
    •  & Jayne S. Danska
  • Article |

    Tussiwand and colleagues show that pDCs develop predominantly from IL-7R+ lymphoid progenitor cells and that mature pDCs are transcriptionally and functionally heterogenous, on the basis of their lymphoid or myeloid lineage.

    • Patrick Fernandes Rodrigues
    • , Llucia Alberti-Servera
    • , Anna Eremin
    • , Gary E. Grajales-Reyes
    • , Robert Ivanek
    •  & Roxane Tussiwand
  • Review Article |

    In this Focus Review, Bar-Or and colleagues discuss the latest evidence that B cells play an important antibody-independent role in multiple sclerosis and the prospects this holds for therapeutic intervention.

    • Rui Li
    • , Kristina R. Patterson
    •  & Amit Bar-Or
  • Article |

    Typhoidal Salmonella is a major pathogen, but there is still a lack of knowledge about suitable vaccine antigens. Cerundolo and colleagues deep-phenotype bacteria-specific CD4+ T cells of Salmonella-infected volunteers to define cross-reactive and serovar-specific responses.

    • Giorgio Napolitani
    • , Prathiba Kurupati
    • , Karen Wei Weng Teng
    • , Malick M. Gibani
    • , Margarida Rei
    • , Anna Aulicino
    • , Lorena Preciado-Llanes
    • , Michael Thomas Wong
    • , Etienne Becht
    • , Lauren Howson
    • , Paola de Haas
    • , Mariolina Salio
    • , Christoph J. Blohmke
    • , Lars Rønn Olsen
    • , David Miguel Susano Pinto
    • , Laura Scifo
    • , Claire Jones
    • , Hazel Dobinson
    • , Danielle Campbell
    • , Helene B. Juel
    • , Helena Thomaides-Brears
    • , Derek Pickard
    • , Dirk Bumann
    • , Stephen Baker
    • , Gordon Dougan
    • , Alison Simmons
    • , Melita A. Gordon
    • , Evan William Newell
    • , Andrew J. Pollard
    •  & Vincenzo Cerundolo
  • Article |

    TCR signaling initiates a signaling cascade involving the kinases Lck and Zap70 and the adaptor LAT. Weiss and colleagues discover a proline-rich motif in LAT, which facilitates interactions among Lck, LAT and Zap70 for efficient TCR signaling.

    • Wan-Lin Lo
    • , Neel H. Shah
    • , Nagib Ahsan
    • , Veronika Horkova
    • , Ondrej Stepanek
    • , Arthur R. Salomon
    • , John Kuriyan
    •  & Arthur Weiss
  • Article |

    The cytokines IL-17A and IL-17F bind via same receptor. Iwakura and colleagues demonstrate different functions for IL-17A and IL-17F in the gut, with the latter altering the production of antimicrobial peptides with consequent effects on the microbiota, the induction of Treg cells and immune-system homeostasis.

    • Ce Tang
    • , Shigeru Kakuta
    • , Kenji Shimizu
    • , Motohiko Kadoki
    • , Tomonori Kamiya
    • , Tomoyuki Shimazu
    • , Sachiko Kubo
    • , Shinobu Saijo
    • , Harumichi Ishigame
    • , Susumu Nakae
    •  & Yoichiro Iwakura
  • Article |

    TIGIT is a co-inhibitory receptor associated with T cell exhaustion. Tian and colleagues demonstrate that TIGIT is the predominant inhibitory receptor on NK cells in both humans and mice and that its blockade enhances NK cell–dependent rejection of tumors in experimental models.

    • Qing Zhang
    • , Jiacheng Bi
    • , Xiaodong Zheng
    • , Yongyan Chen
    • , Hua Wang
    • , Wenyong Wu
    • , Zhengguang Wang
    • , Qiang Wu
    • , Hui Peng
    • , Haiming Wei
    • , Rui Sun
    •  & Zhigang Tian
  • Resource |

    The immune response to pathogens varies substantially among humans. Netea and colleagues show that integration of multi-omics data and deep phenotyping enables prediction of cytokine production in responses to pathogens.

    • Olivier B. Bakker
    • , Raul Aguirre-Gamboa
    • , Serena Sanna
    • , Marije Oosting
    • , Sanne P. Smeekens
    • , Martin Jaeger
    • , Maria Zorro
    • , Urmo Võsa
    • , Sebo Withoff
    • , Romana T. Netea-Maier
    • , Hans J. P. M. Koenen
    • , Irma Joosten
    • , Ramnik J. Xavier
    • , Lude Franke
    • , Leo A. B. Joosten
    • , Vinod Kumar
    • , Cisca Wijmenga
    • , Mihai G. Netea
    •  & Yang Li
  • Article |

    Semaphorins play well-known roles in axon guidance. Kumanogoh and colleagues demonstrate that Semaphorin 6D cell-intrinsically activates anti-inflammatory macrophage polarization.

    • Sujin Kang
    • , Yoshimitsu Nakanishi
    • , Yoshiyuki Kioi
    • , Daisuke Okuzaki
    • , Tetsuya Kimura
    • , Hyota Takamatsu
    • , Shohei Koyama
    • , Satoshi Nojima
    • , Masayuki Nishide
    • , Yoshitomo Hayama
    • , Yuhei Kinehara
    • , Yasuhiro Kato
    • , Takeshi Nakatani
    • , Tomomi Shimogori
    • , Junichi Takagi
    • , Toshihiko Toyofuku
    •  & Atsushi Kumanogoh
  • Technical Report |

    Isolating tissue-resident cells runs the risk of altering their expression profile. Jung and colleagues use a RiboTagging approach to describe the microglial translatome and demonstrate that macrophage extraction from their tissue environment results in significant transcriptional alterations.

    • Zhana Haimon
    • , Alon Volaski
    • , Johannes Orthgiess
    • , Sigalit Boura-Halfon
    • , Diana Varol
    • , Anat Shemer
    • , Simon Yona
    • , Binyamin Zuckerman
    • , Eyal David
    • , Louise Chappell-Maor
    • , Ingo Bechmann
    • , Martin Gericke
    • , Igor Ulitsky
    •  & Steffen Jung