| First Author | Barthels C | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Pages | 14715 | PubMed ID | 28276457 |
| Mgi Jnum | J:244660 | Mgi Id | MGI:5913439 |
| Doi | 10.1038/ncomms14715 | Citation | Barthels C, et al. (2017) CD40-signalling abrogates induction of RORgammat+ Treg cells by intestinal CD103+ DCs and causes fatal colitis. Nat Commun 8:14715 |
| abstractText | 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 gammat+ (RORgammat+) 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 RORgammat+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. |
