Autoimmunity

  • Article
    | Open Access

    T cell receptors are generated by somatic gene recombination, and are normally selected against autoreactivity. Here the authors show that CD4 T cells from patients with autoimmune type 1 diabetes have shorter TCRβ sequences, broader repertoire diversity, and more repertoire sharing than those from healthy individuals.

    • Iria Gomez-Tourino
    • , Yogesh Kamra
    •  & Mark Peakman
  • Article
    | Open Access

    Autoimmune anaemia often accompanies Plasmodium infection and malaria, but how anaemia is induced is still unclear. Here the authors show that Plasmodium DNA, together with interferon-γ, can activate B cells to induce auto-antibodies that recognize red blood cells and promote their removal to contribute to anaemia onset.

    • J. Rivera-Correa
    • , J. J. Guthmiller
    •  & A. Rodriguez
  • Article
    | Open Access

    Follicular helper T (TFH) cells promote germinal centre (GC) response for efficient generation of protective antibodies during humoral immunity. Here the authors show that deficiency of the translational repressor, Capicua/CIC, enhances TFH differentiation and GC responses potentially via the derepression of Etv5.

    • Sungjun Park
    • , Seungwon Lee
    •  & Yoontae Lee
  • Article
    | Open Access

    The protein kinase Lkb1 has been shown to limit conventional T cell activation and pro-inflammatory functions. Here the authors show that Lkb1 also maintains Foxp3 expression and suppressive function in regulatory T (Treg) cells, and that Treg-specific Lkb1-deficient mice develop fatal autoimmune disease.

    • Di Wu
    • , Yuechen Luo
    •  & Xiaoming Feng
  • Article
    | Open Access

    The transcriptional program activated by Smad2/Smad3 is critical for the induction and function of regulatory T cells. Here the authors show that the expression of Smad3 is modulated by the complementary functions of a methyltransferase Ash1l and an lncRNA lnc-Smad3 on the promoter accessibility of the mouseSmad3locus.

    • Meng Xia
    • , Juan Liu
    •  & Xuetao Cao
  • Article
    | Open Access

    IL-17-producing γδ T (γδT17) cells position in barrier tissues but also home to inflammatory sites. How this trafficking is regulated is unclear. Here the authors show that the dynamic expression of chemokine receptors CCR2 and CCR6 differentiates γδT17 cell trafficking patterns at homeostasis and in inflammatory scenarios.

    • Duncan R. McKenzie
    • , Ervin E. Kara
    •  & Shaun R. McColl
  • Article
    | Open Access

    T regulatory (Treg) cells are essential for maintaining immune homeostasis, but how the stability of their lineage and function is regulated is unclear. Here the authors show that Ndfip1 is essential for suppressing Tregcell IL-4 production and metabolic alteration to preserve Treg lineage and function.

    • Awo Akosua Kesewa Layman
    • , Guoping Deng
    •  & Paula M. Oliver
  • Article
    | Open Access

    T helper 17 (Th17) cells can be pathogenic, but what controls this phenotype is unclear. Here the authors show that the transcription factor JunB promotes proinflammatory Th17 function by regulating the transcription of multiple Th17-related genes.

    • Zafrul Hasan
    • , Shin-ichi Koizumi
    •  & Hiroki Ishikawa
  • Article
    | Open Access

    Antibodies against the platelet factor 4 (PF4) support bacterial host defence but in some cases may lead to heparin-induced thrombocytopenia (HIT). Nguyenet al.show that in autoimmune HIT a subset of antibodies binds strongly to PF4 causing its conformational change that leads to association of non-pathogenic PF4 antibodies and thrombotic platelet activation.

    • Thi-Huong Nguyen
    • , Nikolay Medvedev
    •  & Andreas Greinacher
  • Article
    | Open Access

    Neurons can convert pathogenic T cells to anti-inflammatory FoxA1+ regulatory T cells (Tregs), which can ameliorate EAE, but the molecular mechanism is only partially understood. Liu et al. show that autocrine interferon β signalling induces PDL1 expression in neurons, which is essential for neurons to reprogramme pathogenic T cells to FoxA1+ Tregs.

    • Yawei Liu
    • , Andrea Marin
    •  & Shohreh Issazadeh-Navikas
  • Article
    | Open Access

    Ca2+ release-activated Ca2+(CRAC) channels are essential for protective immunity, but the immunological functions of the three ORAI homologues that form CRAC channels are unclear. Here the authors show that ORAI1 and ORAI2 form heteromeric CRAC channels, which fine-tune T cell activation and immune responses.

    • Martin Vaeth
    • , Jun Yang
    •  & Stefan Feske
  • Article
    | Open Access

    The immunosuppressive role of regulatory T (Treg) cells largely depends on their virtue of expressing the transcription factor FOXP3. Here the authors show that the E3 deubiquitinase USP21 stabilizes FOXP3 by mediating its deubiquitination and helps to maintain the expression of Treg signature genes and Treg lineage stability in mice.

    • Yangyang Li
    • , Yue Lu
    •  & Bin Li
  • Article
    | Open Access

    Naïve T cells establish self-tolerance via negative selection of cells with strong reactivity for self-peptide/MHC complexes, but undergo T-cell receptor (TCR) desensitisation when leaving the thymus. Here, Choet al.show that TCR desensitisation correlates with cell-surface density of the phosphatase CD45.

    • Jae-Ho Cho
    • , Hee-Ok Kim
    •  & Jonathan Sprent
  • Article
    | Open Access

    Tiam1 is a guanine nucleotide exchange factor for the Rho-family GTPase Rac1. Here, the authors show that nuclear Tiam1 and Rac1 bind to RORγt on the IL-17 promoter, activating its transcription, and that inhibiting Tiam1/Rac1 is beneficial in a mouse model of autoimmunity.

    • Ahmed T. Kurdi
    • , Ribal Bassil
    •  & Wassim Elyaman
  • Article
    | Open Access

    Type 1 diabetes is driven by T-cell autoimmunity to pancreatic islet cells. Here the authors show that autoreactive anti-IL-2 T and B cells are present in type 1 diabetes patients, and that anti-IL-2 antibodies precede diabetes onset in mice, suggesting their potential as a diagnostic marker.

    • Louis Pérol
    • , John M. Lindner
    •  & Eliane Piaggio
  • Article
    | Open Access

    ICER is a CREM splice variant that represses CREM/CREB signalling. Here the authors use human cells and mouse models of various autoimmune diseases to show that ICER is central to pathogenic Th17 cell differentiation in autoimmunity.

    • Nobuya Yoshida
    • , Denis Comte
    •  & George C. Tsokos
  • Article
    | Open Access

    Roquin is an RNA-binding protein that prevents autoimmunity by limiting expression of receptors such as Ox40. Here, the authors identify an RNA structure that they describe as an alternative decay element, and they characterise its interaction with Roquin using structural and biochemical techniques.

    • Robert Janowski
    • , Gitta A. Heinz
    •  & Michael Sattler
  • Article
    | Open Access

    Autoimmune brain inflammation is associated with activation of macrophages and microglia. Here the authors show that fibrinogen induces encephalitogenic T-cell activation and macrophage recruitment to the central nervous system, and promotes demyelination in a mouse model of multiple sclerosis.

    • Jae Kyu Ryu
    • , Mark A. Petersen
    •  & Katerina Akassoglou
  • Article
    | Open Access

    T cells that are activated by self-antigens in the periphery can migrate into the brain causing neuroinflammatory disease. Here the authors show that TBK1 is necessary for activated T-cell egress from the lymph node, and blocking TBK1 ameliorates autoimmunity in a mouse model of multiple sclerosis.

    • Jiayi Yu
    • , Xiaofei Zhou
    •  & Shao-Cong Sun
  • Article |

    Whether differentiation of regulatory and conventional T cells in the thymus requires similar T-cell receptor affinity is not known. Here, the authors show that cells expressing the same T-cell receptor selected on the same ligand can give rise to both lineages, but different sensitivity to negative selection separates their T-cell receptor repertoires.

    • Lukasz Wojciech
    • , Alicja Ignatowicz
    •  & Leszek Ignatowicz
  • Article
    | Open Access

    Regulatory T cells (Tregs) are important for the maintenance of self-tolerance and this requires their trafficking to the lymph nodes and target tissues. Here, the authors show that the recognition of self-antigens expressed by endothelial cells in target tissue is instrumental for efficient Treg recruitment in vivo.

    • Hongmei Fu
    • , Madhav Kishore
    •  & Federica M. Marelli-Berg
  • Article |

    Single nucleotide polymorphisms in the gene encoding the protein phosphatase PTPN2 are associated with autoimmunity in humans. Here, Wiede et al. show that PTPN2 suppresses the proliferative capacity of T cells in lymphopenia and prevents the development of autoimmunity resulting from overt homoeostatic proliferation.

    • Florian Wiede
    • , Nicole L. La Gruta
    •  & Tony Tiganis
  • Article |

    Autoimmune T cell receptors can interact with both self and microbial antigens, but the structural basis for crossreactivity is not fully understood. Here, the authors provide structural insights into binding characteristics of the autoreactive T cell receptor Hy.1B11 to both self and pathogen-derived peptides.

    • Dhruv K. Sethi
    • , Susana Gordo
    •  & Kai W. Wucherpfennig