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CD40-signalling abrogates induction of RORγt+ Treg cells by intestinal CD103+ DCs and causes fatal colitis

Author

Listed:
  • Christian Barthels

    (Institute for Immunology, LMU Munich)

  • Ana Ogrinc

    (Institute for Immunology, LMU Munich)

  • Verena Steyer

    (Institute for Immunology, LMU Munich)

  • Stefanie Meier

    (Institute for Immunology, LMU Munich)

  • Ferdinand Simon

    (Institute for Immunology, LMU Munich)

  • Maria Wimmer

    (Center of Allergy Environment (ZAUM), Helmholtz Center and TU Munich)

  • Andreas Blutke

    (Section of Animal Pathology, LMU Munich)

  • Tobias Straub

    (Bioinformatics core unit, BMC, LMU Munich)

  • Ursula Zimber-Strobl

    (Helmholtz Zentrum München, Research Unit Gene Vectors)

  • Esther Lutgens

    (Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, LMU Munich
    AMC)

  • Peggy Marconi

    (University of Ferrara)

  • Caspar Ohnmacht

    (Center of Allergy Environment (ZAUM), Helmholtz Center and TU Munich)

  • Debora Garzetti

    (Max von Pettenkofer Institute of Hygiene and Medical Microbiology, German Center for Infection Research (DZIF), Partner Site Munich, LMU Munich)

  • Bärbel Stecher

    (Max von Pettenkofer Institute of Hygiene and Medical Microbiology, German Center for Infection Research (DZIF), Partner Site Munich, LMU Munich)

  • Thomas Brocker

    (Institute for Immunology, LMU Munich)

Abstract

Immune homeostasis in intestinal tissues depends on the generation of regulatory T (Treg) cells. CD103+ dendritic cells (DCs) acquire microbiota-derived material from the gut lumen for transport to draining lymph nodes and generation of receptor-related orphan γt+ (RORγt+) Helios−-induced Treg (iTreg) cells. Here we show CD40-signalling as a microbe-independent signal that can induce migration of CD103+ DCs from the lamina propria (LP) to the mesenteric lymph nodes. Transgenic mice with constitutive CD11c-specific CD40-signalling have reduced numbers of CD103+ DCs in LP and a low frequency of RORγt+Helios− iTreg cells, exacerbated inflammatory Th1/Th17 responses, high titres of microbiota-specific immunoglobulins, dysbiosis and fatal colitis, but no pathology is detected in other tissues. Our data demonstrate a CD40-dependent mechanism capable of abrogating iTreg cell induction by DCs, and suggest that the CD40L/CD40-signalling axis might be able to intervene in the generation of new iTreg cells in order to counter-regulate immune suppression to enhance immunity.

Suggested Citation

  • Christian Barthels & Ana Ogrinc & Verena Steyer & Stefanie Meier & Ferdinand Simon & Maria Wimmer & Andreas Blutke & Tobias Straub & Ursula Zimber-Strobl & Esther Lutgens & Peggy Marconi & Caspar Ohnm, 2017. "CD40-signalling abrogates induction of RORγt+ Treg cells by intestinal CD103+ DCs and causes fatal colitis," Nature Communications, Nature, vol. 8(1), pages 1-13, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14715
    DOI: 10.1038/ncomms14715
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