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Barthels, C.* ; Ogrinc, A.* ; Steyer, V.* ; Meier, S.* ; Simon, F.* ; Wimmer, M. ; Blutke, A.* ; Straub, T.* ; Zimber-Strobl, U. ; Lutgens, E.* ; Marconi, P.* ; Ohnmacht, C. ; Garzetti, D.* ; Stecher, B.* ; Brocker, T.*

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

Nat. Commun. 8:14715 (2017)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Regulatory T-cells; Classical Dendritic Cells; In-vivo; Integrin Alpha-v-beta-8; Signaling Controls; Retinoic-acid; Th17 Cells; Reg-cells; B-cells; Immunity
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Quellenangaben Volume: 8, Issue: , Pages: , Article Number: 14715 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed