| First Author | Yan Y | Year | 2021 |
| Journal | Immunity | Volume | 54 |
| Issue | 3 | Pages | 499-513.e5 |
| PubMed ID | 33691135 | Mgi Jnum | J:305830 |
| Mgi Id | MGI:6706574 | Doi | 10.1016/j.immuni.2021.02.002 |
| Citation | Yan Y, et al. (2021) Interleukin-6 produced by enteric neurons regulates the number and phenotype of microbe-responsive regulatory T cells in the gut. Immunity 54(3):499-513.e5 |
| abstractText | The immune and enteric nervous (ENS) systems monitor the frontier with commensal and pathogenic microbes in the colon. We investigated whether FoxP3(+) regulatory T (Treg) cells functionally interact with the ENS. Indeed, microbe-responsive RORgamma(+) and Helios(+) subsets localized in close apposition to nitrergic and peptidergic nerve fibers in the colon lamina propria (LP). Enteric neurons inhibited in vitro Treg (iTreg) differentiation in a cell-contact-independent manner. A screen of neuron-secreted factors revealed a role for interleukin-6 (IL-6) in modulating iTreg formation and their RORgamma(+) proportion. Colonization of germfree mice with commensals, especially RORgamma(+) Treg inducers, broadly diminished colon neuronal density. Closing the triangle, conditional ablation of IL-6 in neurons increased total Treg cells but decreased the RORgamma(+) subset, as did depletion of two ENS neurotransmitters. Our findings suggest a regulatory circuit wherein microbial signals condition neuronal density and activation, thus tuning Treg cell generation and immunological tolerance in the gut. |
