T-bet controls intestinal mucosa immune responses via repression of type 2 innate lymphoid cell function.
T-bet controls intestinal mucosa immune responses via repression of type 2 innate lymphoid cell function.
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DOI：
10.1038/s41385-018-0092-6
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发表时间：
2019-01
影响因子：
8
通讯作者：
Lord GM
中科院分区：
文献类型：
--
作者：
Garrido-Mesa N;Schroeder JH;Stolarczyk E;Gallagher AL;Lo JW;Bailey C;Campbell L;Sexl V;MacDonald TT;Howard JK;Grencis RK;Powell N;Lord GM
先天性淋巴样细胞（ILC）在调节粘膜表面的免疫应答中起重要作用。转录因子T-bet对ILC 1和NCR+ ILC 3的功能至关重要，T-bet的组成性缺失阻止了这些子集的发展。在缺乏适应性免疫系统的情况下缺乏T-bet导致由于异常ILC 3应答而发生微生物群依赖性结肠炎。因此，先天免疫系统中的T-bet表达被认为抑制致病性免疫应答。在这里，我们表明，T-bet发挥了意想不到的作用，在负调节先天性2型反应，否则完整的免疫系统的背景下。ILC中T-bet的选择性丢失导致ILC 2的扩增和活性增加，这对粘膜免疫具有重要的功能影响，包括增强对旋毛虫感染和炎性结肠炎的保护。从机制上讲，我们表明T-bet通过调节IL-7受体信号传导来控制肠道ILC池。这些数据表明，T-bet在ILC中的表达作为调节致病性与保护性粘膜免疫应答的关键转录检查点，这对于理解炎性肠病和肠道感染的发病机制具有重要意义。
Innate lymphoid cells (ILCs) play an important role in regulating immune responses at mucosal surfaces. The transcription factor T-bet is crucial for the function of ILC1s and NCR+ ILC3s and constitutive deletion of T-bet prevents the development of these subsets. Lack of T-bet in the absence of an adaptive immune system causes microbiota-dependent colitis to occur due to aberrant ILC3 responses. Thus, T-bet expression in the innate immune system has been considered to dampen pathogenic immune responses. Here, we show that T-bet plays an unexpected role in negatively regulating innate type 2 responses, in the context of an otherwise intact immune system. Selective loss of T-bet in ILCs leads to the expansion and increased activity of ILC2s, which has a functionally important impact on mucosal immunity, including enhanced protection from Trichinella spiralis infection and inflammatory colitis. Mechanistically, we show that T-bet controls the intestinal ILC pool through regulation of IL-7 receptor signalling. These data demonstrate that T-bet expression in ILCs acts as the key transcriptional checkpoint in regulating pathogenic vs. protective mucosal immune responses, which has significant implications for the understanding of the pathogenesis of inflammatory bowel diseases and intestinal infections.
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影响因子：
8
作者：
Califano D;Furuya Y;Roberts S;Avram D;McKenzie ANJ;Metzger DW
通讯作者：
Metzger DW
影响因子：
16.6
作者：
通讯作者：
--
DOI：
10.4049/jimmunol.1300379
发表时间：
2013-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Furusawa J;Moro K;Motomura Y;Okamoto K;Zhu J;Takayanagi H;Kubo M;Koyasu S
通讯作者：
Koyasu S
影响因子：
64.5
作者：
Karo JM;Schatz DG;Sun JC
通讯作者：
Sun JC
影响因子：
5.4
作者：
Comalada, M;Camuesco, D;Zarzuelo, A
通讯作者：
Zarzuelo, A