AHR 通过依赖和不依赖于 Notch 的途径驱动肠道 ILC22 细胞和出生后淋巴组织的发育。
AHR drives the development of gut ILC22 cells and postnatal lymphoid tissues via pathways dependent on and independent of Notch.
机构信息
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
出版信息
Nat Immunol. 2011 Nov 20;13(2):144-51. doi: 10.1038/ni.2187.
Abstract
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.
摘要
固有淋巴细胞 (ILC) 中的 ILC22 型通过分泌白细胞介素 22 (IL-22) 来保护肠道黏膜免受感染。ILC22 细胞包括 NKp46(+)和淋巴组织诱导 (LTi)-样亚群，这些亚群表达芳香烃受体 (AHR)。在这里，我们发现 Ahr(-/-) 小鼠的 ILC22 细胞数量明显减少，导致 IL-22 分泌不足，对肠道细菌感染的保护作用不足。Ahr(-/-) 小鼠还缺乏出生后“印迹”的隐窝斑和孤立的淋巴滤泡 (ILFs)，但不缺乏胚胎“印迹”的派尔集合淋巴结。AHR 诱导转录因子 Notch，这是 NKp46(+) ILC 所必需的，而 LTi-样 ILC 、隐窝斑和 ILFs 部分依赖于 Notch 信号。因此，AHR 对于 ILC22 细胞和出生后肠道淋巴组织是必不可少的。此外，ILC22 亚群在 Notch 的需求和对肠道淋巴组织生成的影响上存在异质性。
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