Immune tolerance articles within Nature Communications

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  • Article
    | Open Access

    Il-10-expressing B cells play a pivotal role in immune homeostasis, but little is known about the factors and pathways that affect the development of this heterologous population of regulatory B cells. Here authors show in a mouse model that in embryonic life, soluble IgM restrains the expansion of Il-10-positive B cells, via utilizing FcµR and other putative receptors.

    • Shannon Eileen McGettigan
    • , Lazaro Emilio Aira
    •  & Gudrun F. Debes

  • Article
    | Open Access

    Environmental factors such as diet have been shown to be involved with the development of colitis. Here the authors show that L-tryptophan promotes the development of GPR15+ Treg cells via the host IDO1/2 pathway and that tryptophan consumption in mice reduces severity of colitis in a C. rodentium mouse model.

    • Nguyen T. Van
    • , Karen Zhang
    •  & Sangwon V. Kim

  • Article
    | Open Access

    Increasing evidence suggests that antigen presentation by B cells is critical to the initiation of autoimmunity. Here, the authors demonstrate that tolerance breakdown is initiated outside of germinal centres and that B cells can directly instruct T cells to break tolerance and propagate autoimmune responses.

    • Cecilia Fahlquist-Hagert
    • , Thomas R. Wittenborn
    •  & Søren E. Degn

  • Article
    | Open Access

    NBEAL2 loss of function mutations lead to grey platelet syndrome, a condition characterised by α-granule-deficient platelets and, in a proportion of cases, by autoimmunity. Here authors show that NBEAL2 physically interacts with CTLA-4 in human T cells, and NBEAL2 deficiency leads to reduced CTLA-4 surface expression in effector T cells, but not regulatory T cells, thus tipping the balance towards autoimmunity.

    • Laure Delage
    • , Francesco Carbone
    •  & Frédéric Rieux-Laucat

  • Article
    | Open Access

    The blockade of CD28 signalling is known to reduce pathological T cell responses in the context of both autoimmunity and transplantation, but has been associated with impairment of the regulatory T cell compartment. Here the authors show combining costimulation blockade with the administration of interleukin 2 selectively impairs the T effector response whilst maintaining the regulatory T cell pool and suggest functional effect in a murine model of autoimmune diabetes.

    • Chun Jing Wang
    • , Lina Petersone
    •  & Lucy S. K. Walker

  • Article
    | Open Access

    Regulatory T (Treg) cells have been implicated in the induction of airway tolerance and amelioration of respiratory duct inflammation. Here the authors show, using PD-L2 deficient mice, that the immune suppression signal from PD-L2 is important for modulating Treg cell metabolism and function for proper induction of respiratory tolerance in mice.

    • Benjamin P. Hurrell
    • , Doumet Georges Helou
    •  & Omid Akbari

  • Article
    | Open Access

    The thymus generates all T cells, including those that underly autoimmune diseases. Here, using deep sequencing, the authors profile human medullary thymic epithelial cells and establish a web portal to query their transcriptome, which may serve as a tool to help identify the drivers of autoimmunity.

    • Jason A. Carter
    • , Léonie Strömich
    •  & Hannah V. Meyer

  • Article
    | Open Access

    Follicular T cells regulate germinal centre reactions, but their phenotypes in autoimmune disease are unclear. Using a mouse model of autoantibody disease, the authors show that autoimmune follicular T cells differ by TCR clonotype and transcriptional profile from non-autoimmune follicular T cells.

    • Elliot H. Akama-Garren
    • , Theo van den Broek
    •  & Michael C. Carroll

  • Article
    | Open Access

    T cells are selected in the thymus, through interaction with self-antigens, to remove autoreactive cells. Here the authors show that a specialized thymic dendritic cell subset juxtaposes to microvessels, requires CX3CR1/CX3CL1 for this positioning, and has processes extruding into the blood stream to sample soluble macromolecules and assist in T cell selection.

    • Elisabeth H. Vollmann
    • , Kristin Rattay
    •  & Ulrich H. von Andrian

  • Article
    | Open Access

    The thymus supports T cell immunity by providing the environment for thymocyte differentiation. Here the authors profile human thymic stroma at the single cell level, identifying ionocytes as a new medullary population and defining tissue specific antigen expression in multiple stromal cell types.

    • Jhoanne L. Bautista
    • , Nathan T. Cramer
    •  & Audrey V. Parent

  • Article
    | Open Access

    B7-CD28 co-stimulation is important for T cell activation and clonal expansion in the periphery. Here the authors show that, in mouse thymus, B7-CD28 differentially controls thymocyte clonal deletion and Treg induction, with distinct CD28 signaling domains and B7-expressing antigen presenting cells mediating these two processes.

    • Masashi Watanabe
    • , Ying Lu
    •  & Richard J. Hodes

  • Article
    | Open Access

    T cell tolerance is established in the thymus via interactions with medullary thymic epithelial cells (mTEC) expressing tissue-restricted self antigens. Here, the authors suggest, using new transgenic mouse lines and single cell transcriptome analyses, that specific mTEC subsets are associated with distinct T cell fates.

    • Marie-Ève Lebel
    • , Marie Coutelier
    •  & Heather J. Melichar

  • Article
    | Open Access

    Immune tolerance is mediated by the deletion of autoreactive T cells via medullary thymic epithelial cells (mTEC) and dendritic cells (DC), and by the induction of regulatory T cells (Treg). Here the authors show that mTEC receiving toll-like receptor signaling control the recruitment of CD14+Sirpα+ DC population that is capable of inducing Treg for establishing tolerance.

    • Matouš Vobořil
    • , Tomáš Brabec
    •  & Dominik Filipp

  • Article
    | Open Access

    TIGIT is a lymphocyte co-inhibitory receptor that can limit type 1 and cytotoxic T cell responses and maintain immunological tolerance. Here the authors show that TIGIT also limits immune pathology during LCMV or influenza infections in mice by driving IL-10 expression without negatively affecting the viral load.

    • Michelle Schorer
    • , Nikolas Rakebrandt
    •  & Nicole Joller

  • Article
    | Open Access

    Elucidation of broadly neutralizing antibodies (bnAb) is a goal in HIV vaccine development. Here, Bradley et al. show that administration of CTLA-4 blocking antibody with vaccine antigens increases HIV-1 envelope antibody responses in macaques and a bnAb precursor mouse model.

    • Todd Bradley
    • , Masayuki Kuraoka
    •  & Barton F. Haynes

  • Article
    | Open Access

    . TGFβ is critical for limiting autoreactive responses of peripheral T cells. Here, the authors show that TGFβ signaling in thymocytes mediates elimination of self-reactive T cells and promotes the expression of self-antigens by medullary thymic epithelial cells.

    • Mark J. McCarron
    • , Magali Irla
    •  & Julien C. Marie

  • Article
    | Open Access

    T cells from narcolepsy patients were recently reported to recognize hypocretin, a wakefulness-promoting neurohormone, suggesting autoimmune origin of the disease. Here the authors show that hypocretin-specific T cells expand both in healthy controls and in narcolepsy patients, and identify preliminary features that may distinguish them.

    • Wei Jiang
    • , James R. Birtley
    •  & Elizabeth D. Mellins

  • Article
    | Open Access

    B-1a B cells are innate-like cells with biased reactivity to bacteria and self-antigens. Here the authors show that reduced interleukin-7 in developing fetal liver-derived pro-B cells induces premature immunoglobulin κ rearrangement, alleviating the requirement for a pre-BCR selection stage and allowing the generation of autoreactive B1-a B cells.

    • Jason B. Wong
    • , Susannah L. Hewitt
    •  & Jane A. Skok

  • Article
    | Open Access

    Injection of donor apoptotic cells induces graft tolerance in mice. Here the authors combine this approach with short immunosuppressive therapy to achieve long-term tolerance to allogeneic islets and restoration of normoglycemia in diabetic nonhuman primates, and delineate cellular and molecular correlates of tolerance induction.

    • Amar Singh
    • , Sabarinathan Ramachandran
    •  & Bernhard J. Hering

  • Article
    | Open Access

    Autoreactive T cells are deleted in the thymus via thymic negative selection and Bim-mediated apoptosis. Here the authors identify a cis-acting enhancer, EBAB, that is essential for proper Bim expression and apoptosis induction, and show that EBAB deficiency specifically impairs thymic negative selection without affecting peripheral T cell homeostasis.

    • Miki Arai Hojo
    • , Kyoko Masuda
    •  & Shinpei Kawaoka

  • Article
    | Open Access

    Both thymic epithelial cells and dendritic cells present self antigens in the thymus to mediate thymic selection and T cell tolerance. Here the authors quantify, using two-photon live imaging of mouse thymic slices, the relative contribution of these two cell types, as well as the effects of antigen cross-presentation by dendritic cells, during tolerance induction.

    • J. N. Lancaster
    • , H. M. Thyagarajan
    •  & L. I. R. Ehrlich

  • Article
    | Open Access

    The inhibitory receptor, FcγRIIb, is reported to limit autoimmune B cell response. Here the authors show that FcγRIIb has a dual role in both human and mouse, with reduced FcγRIIb expression or function associated with enhanced pre-immune B cell tolerance, yet defective control of mature autoreactive B cells in the germinal center.

    • Marion Espéli
    • , Rachael Bashford-Rogers
    •  & Kenneth G. C. Smith

  • Article
    | Open Access

    Autoreactive T cells are suspected to destroy hypocretin-producing neurons in narcolepsy. Here the authors detect CD8 T cells recognizing narcolepsy-related proteins in healthy individuals and in patients with narcolepsy, and show that the frequency of self-reactive CD8 T cells differs between patients and controls sharing the same HLA-II risk allele.

    • Natasja Wulff Pedersen
    • , Anja Holm
    •  & Birgitte Rahbek Kornum

  • Article
    | Open Access

    Transplantation of allogeneic bone marrow helps establish chimerism that may induce tolerance to tissue grafts. Here the authors show that a CD117-antibody-drug-conjugate helps precondition the recipients for inducing mixed chimerism and allo-tolerance without clear adverse effects or the need for chronic immune suppression.

    • Zhanzhuo Li
    • , Agnieszka Czechowicz
    •  & Philip M. Murphy

  • Article
    | Open Access

    The transcription factor Foxp3 and Stat5 modulate lineage stability and function of regulatory T (Treg) cells to promote immune homeostasis. Here the authors show that O-GlcNAcylation of Foxp3 and Stat5, mediated by O-GlcNAc transferase (OGT), is essential for Treg-mediate immune balance, with Treg-specific deficiency of OGT leading to severe autoimmunity.

    • Bing Liu
    • , Oscar C. Salgado
    •  & Hai-Bin Ruan

  • Article
    | Open Access

    Regulatory T (Treg) cells are developed in the thymus, and are essential for suppressing detrimental autoimmunity. Here the authors show, using mice with dampened interleukin 2 (IL-2) signaling, that IL-2 helps position the pioneer factor SATB1 to control genome-wide chromatin accessibility to facilitate Treg cell lineage commitment in the thymus.

    • Laurent Chorro
    • , Masako Suzuki
    •  & Grégoire Lauvau

  • Article
    | Open Access

    Antigen present and presented in the structures of the skin can result in immune responses that elicit tolerance, protective immunity or allergy, depending on the immunological context. Here the authors describe a key role for the hair follicle and CD11b+ dendritic cells in the priming of local antigenic tolerance.

    • Leticia Tordesillas
    • , Daniel Lozano-Ojalvo
    •  & M. Cecilia Berin

  • Article
    | Open Access

    Induction of tolerance in the gut relies on immunomodulatory functions of mesenteric lymph nodes (mLN). Here the authors show that mLN stromal cells receive early microbiota imprinting in the neonatal phase to exhibit long-term, location-specific transcriptional programs for the induction of regulatory T cells and peripheral tolerance.

    • Joern Pezoldt
    • , Maria Pasztoi
    •  & Jochen Huehn

  • Article
    | Open Access

    Donor-derived dendritic cells (do-DC) in the graft can contribute to the induction of alloimmunity and tissue rejection, but how do-DC can be targeted for improving graft survival is unclear. Here the authors show that reducing MHC-II expression on do-DCs by DnaK pre-treatment can decrease the priming of alloimmunity and prolong graft survival in mouse models.

    • Thiago J. Borges
    • , Naoka Murakami
    •  & Cristina Bonorino

  • Article
    | Open Access

    Autoreactive T cells are removed during their development in the thymus through the functions of medullary thymic epithelial cells (mTEC) and dendritic cells (DC), a process termed negative selection. Here the authors show that mTEC-T cell crosstalk and lymphotoxin α signalling are essential for the proper recruitment of DCs into the thymus.

    • Noëlla Lopes
    • , Jonathan Charaix
    •  & Magali Irla

  • Article
    | Open Access

    Engineered T cells with chimeric antigen receptor (CAR) are emerging as an effective cancer therapy. Here the authors show that CAR T cells recognizing self-MHC can be ‘tuned’ ex vivo via CAR downregulation and CAR T cell death to generate a CAR T pool specifically targeting tumor cells with high MHC expression.

    • Chungyong Han
    • , Su-Jung Sim
    •  & Byoung S. Kwon

  • Article
    | Open Access

    Post-translational modifications are associated with autoimmune diseases but definitive evidence of their contribution to escape from central tolerance mechanisms is needed. Here, the authors show that T cells specific for post-translational modifications of type II collagen escape intrathymic tolerance induction in a mouse model of rheumatoid arthritis.

    • Bruno Raposo
    • , Patrick Merky
    •  & Johan Bäcklund

  • Article
    | Open Access

    The RNA-binding proteins Roquin-1 and Roquin-2 are essential for immune cell function and postnatal survival in mice. Here, the authors identify NUFIP2 as a cofactor of Roquin; Roquin binds and stabilizes NUFIP2 in cells while NUFIP2 regulates Roquin mRNA target recognition.

    • Nina Rehage
    • , Elena Davydova
    •  & Vigo Heissmeyer

  • Article
    | Open Access

    Non-circulating, tissue-resident T cells have been reported for non-lymphoid organs, but their characterization and regulation in secondary lymphoid organs (SLO) are still lacking. Here the authors show that age and microbiota both exert SLO-specific effects for the various tissue-resident T cell subsets.

    • Aurélie Durand
    • , Alexandra Audemard-Verger
    •  & Bruno Lucas

  • Article
    | Open Access

    An efficient HIV-1 vaccine will likely depend on eliciting broadly neutralizing antibodies (bnAb). Here the authors analyze the B cell repertoire in macaques and knock-in mice in response to sequential immunization with Env variants that induce a bnAb targeting the CD4-binding site of Env in a HIV-1 infected individual.

    • Wilton B. Williams
    • , Jinsong Zhang
    •  & Laurent Verkoczy

  • Article
    | Open Access

    CD103+ dendritic cells induce iTreg cells to maintain immune balance in the gut, but how CD40-signalling regulates this process is unclear. Here the authors show that mice with constitutive CD11c-specific CD40-signalling have altered CD103+dendritic cell migration, reduced iTreg cell induction, and fatal colitis.

    • Christian Barthels
    • , Ana Ogrinc
    •  & Thomas Brocker

  • Article
    | Open Access

    Self-reactive B cells that are anergic express mainly IgD, yet the function of IgD is not clear. Here the authors analyse primary B cells from mice to show that IgD signalling attenuates self-antigen induced gene expression and promotes survival of anergic B cells that might go on to reactivate to foreign antigens and mutate away from self-reactivity.

    • Zahra Sabouri
    • , Samuel Perotti
    •  & Christopher C. Goodnow

  • Article |

    Self-reactive B cells producing autoantibodies are associated with autoimmune conditions. Here, the authors show that in mice lacking the surrogate light chain, which normally assembles with antibody heavy chain to form a pre-B-cell receptor, the autoantibody-producing cells derive from germinal centres.

    • Ola Grimsholm
    • , Weicheng Ren
    •  & Inga-Lill Mårtensson

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