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, 2021 03 09.
Article
en En
| MEDLINE
| ID: mdl-33691135
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 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Subgrupos de Linfocitos T
/
Interleucina-6
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Linfocitos T Reguladores
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Sistema Nervioso Entérico
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Intestinos
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Neuronas
Límite:
Animals
Idioma:
En
Revista:
Immunity
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos