The aryl hydrocarbon receptor regulates gut immunity through modulation of innate lymphoid cells.
Immunity
; 36(1): 92-104, 2012 Jan 27.
Article
em En
| MEDLINE
| ID: mdl-22177117
ABSTRACT
Innate lymphoid cells (ILCs) expressing the nuclear receptor RORγt are essential for gut immunity presumably through production of interleukin-22 (IL-22). The molecular mechanism underlying the development of RORγt(+) ILCs is poorly understood. Here, we have shown that the aryl hydrocarbon receptor (Ahr) plays an essential role in RORγt(+) ILC maintenance and function. Expression of Ahr in the hematopoietic compartment was important for accumulation of adult but not fetal intestinal RORγt(+) ILCs. Without Ahr, RORγt(+) ILCs had increased apoptosis and less production of IL-22. RORγt interacted with Ahr and promoted Ahr binding at the Il22 locus. Upon IL-23 stimulation, Ahr-deficient RORγt(+) ILCs had reduced IL-22 expression, consistent with downregulation of IL-23R in those cells. Ahr-deficient mice succumbed to Citrobacter rodentium infection, whereas ectopic expression of IL-22 protected animals from early mortality. Our data uncover a previously unrecognized physiological role for Ahr in promoting innate gut immunity by regulating RORγt(+) ILCs.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos
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Interleucinas
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Receptores de Hidrocarboneto Arílico
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Trato Gastrointestinal
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Imunidade Inata
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article