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EnglishImmune 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.
| Data di pubblicazione: | 2017 | |
| Titolo: | CD40-signalling abrogates induction of RORγt+ Treg cells by intestinal CD103+ DCs and causes fatal colitis | |
| Autori: | Barthels, C; Ogrinc, A; Steyer, V; Meier, S; Simon, F; Wimmer, M; Blutke, A; Straub, T; Zimber Strobl, U; Lutgens, E; Marconi, Peggy Carla Raffaella; Ohnmacht, C; Garzetti, D; Stecher, B; Brocker, T. | |
| Rivista: | NATURE COMMUNICATIONS | |
| 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 | |
| Abstract in inglese: | 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. | |
| Digital Object Identifier (DOI): | 10.1038/ncomms14715 | |
| Handle: | http://hdl.handle.net/11392/2368106 | |
| Appare nelle tipologie: | 03.1 Articolo su rivista |
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