AHR drives the development of gut ILC22 cells and postnatal lymphoid tissues via pathways dependent on and independent of Notch

被引：630

作者：

Lee, Jacob S. ^{[1
]}

Cella, Marina ^{[1
]}

McDonald, Keely G. ^{[2
]}

Garlanda, Cecilia ^{[3
]}

Kennedy, Gregory D. ^{[4
]}

Nukaya, Manabu ^{[4
]}

Mantovani, Alberto ^{[3
,5
]}

Kopan, Raphael ^{[6
]}

Bradfield, Christopher A. ^{[7
]}

Newberry, Rodney D. ^{[2
]}

Colonna, Marco ^{[1
]}

机构：

[1] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA

[2] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA

[3] Inst Ricovero & Cura Carattere Sci, Ist Clin Humanitas, Lab Immunol & Inflammat, Rozzano, Italy

[4] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI USA

[5] Univ Milan, Dept Translat Med, Rozzano, Italy

[6] Washington Univ, Sch Med, Dept Dev Biol & Med, St Louis, MO USA

[7] Univ Wisconsin, McArdle Lab Canc Res, Sch Med & Publ Hlth, Madison, WI 53706 USA

来源：

NATURE IMMUNOLOGY | 2012年 / 13卷 / 02期

基金：

美国国家卫生研究院;

关键词：

ARYL-HYDROCARBON RECEPTOR; ROR-GAMMA-T; INTESTINAL HOMEOSTASIS; DIFFERENTIATION; INFLAMMATION; LIGAND; IL-22; MOUSE; IL-17; ACTIVATION;

D O I：

10.1038/ni.2187

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Innate lymphoid cells (ILCs) of the ILC22 type protect the intestinal mucosa from infection by secreting interleukin 22 (IL-22). ILC22 cells include NKp46(+) and lymphoid tissue-inducer (LTi)-like subsets that express the aryl hydrocarbon receptor (AHR). Here we found that Ahr(-/-) mice had a considerable deficit in ILC22 cells that resulted in less secretion of IL-22 and inadequate protection against intestinal bacterial infection. Ahr(-/-) mice also lacked postnatally 'imprinted' cryptopatches and isolated lymphoid follicles (ILFs), but not embryonically 'imprinted' Peyer's patches. AHR induced the transcription factor Notch, which was required for NKp46(+) ILCs, whereas LTi-like ILCs, cryptopatches and ILFs were partially dependent on Notch signaling. Thus, AHR was essential for ILC22 cells and postnatal intestinal lymphoid tissues. Moreover, ILC22 subsets were heterogeneous in their requirement for Notch and their effect on the generation of intestinal lymphoid tissues.

引用

页码：144 / U58

页数：9

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