@article {1587242,
	title = {Interleukin-6 produced by enteric neurons regulates the number and phenotype of microbe-responsive regulatory T cells in the gut},
	journal = {Immunity},
	volume = {54},
	number = {3},
	year = {2021},
	month = {2021 Mar 09},
	pages = {499-513.e5},
	abstract = {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 RORγ and Helios subsets localized in close apposition to nitrergic and peptidergic nerve fibers in the colon lamina propria (LP). Enteric neurons inhibited in\&nbsp;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 RORγ proportion. Colonization of germfree mice with commensals, especially RORγ Treg inducers, broadly diminished colon neuronal density. Closing the triangle, conditional ablation of IL-6 in neurons increased total Treg cells but decreased the RORγ 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.},
	issn = {1097-4180},
	doi = {10.1016/j.immuni.2021.02.002},
	author = {Yan, Yiqing and Ramanan, Deepshika and Rozenberg, Milena and McGovern, Kelly and Rastelli, Daniella and Vijaykumar, Brinda and Yaghi, Omar and Voisin, Tiphaine and Mosaheb, Munir and Chiu, Isaac and Itzkovitz, Shalev and Rao, Meenakshi and Mathis, Diane and Benoist, Christophe}
}
