Epidermal Growth Factor Receptor Expression Licenses Type-2 Helper T Cells to Function in a T Cell Receptor-Independent Fashion.
Epidermal Growth Factor Receptor Expression Licenses Type-2 Helper T Cells to Function in a T Cell Receptor-Independent Fashion.
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DOI：
10.1016/j.immuni.2017.09.013
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发表时间：
2017-10-17
期刊：
影响因子：
32.4
通讯作者：
Zaiss DM
中科院分区：
文献类型：
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作者：
Minutti CM;Drube S;Blair N;Schwartz C;McCrae JC;McKenzie AN;Kamradt T;Mokry M;Coffer PJ;Sibilia M;Sijts AJ;Fallon PG;Maizels RM;Zaiss DM
胃肠道蠕虫感染触发白细胞介素-33（IL-33）的释放，其诱导感染部位的2型辅助T细胞（Th 2细胞）产生IL-13，从而以T细胞受体（TCR）非依赖性方式促进宿主抗性。在这里，我们表明，作为IL-33诱导的IL-13分泌的先决条件，Th 2细胞需要表皮生长因子受体（EGFR）及其配体双调蛋白的表达，以形成T1/ST 2（IL-33 R）和EGFR之间的信号复合物。这种共享的信号复合物允许IL-33诱导EGFR介导的MAP-激酶信号通路的活化，并因此诱导IL-13的表达。T细胞上EGFR表达的缺乏废除了感染组织中的IL-13表达并损害了宿主抗性。EGFR在Th 2细胞上的表达是TCR信号传导依赖性的，因此，我们的数据揭示了抗原呈递控制Th 2细胞在炎症部位的先天效应子功能的机制。T细胞上缺乏EGFR表达的小鼠对蠕虫感染更敏感EGFR与T1/ST 2形成复合物，允许IL-33诱导的IL-13表达双调蛋白介导的EGFR活化对于与T1/ST 2形成复合物是必需的EGFR表达由TCR接合诱导并由细胞因子如TSLP维持。Minutti等人现在表明TCR诱导的EGFR及其配体双调蛋白的表达对于IL-33诱导的IL-13分泌是必需的，揭示了抗原特异性活化控制Th 2细胞的先天效应子功能的机制。
Gastro-intestinal helminth infections trigger the release of interleukin-33 (IL-33), which induces type-2 helper T cells (Th2 cells) at the site of infection to produce IL-13, thereby contributing to host resistance in a T cell receptor (TCR)-independent manner. Here, we show that, as a prerequisite for IL-33-induced IL-13 secretion, Th2 cells required the expression of the epidermal growth factor receptor (EGFR) and of its ligand, amphiregulin, for the formation of a signaling complex between T1/ST2 (the IL-33R) and EGFR. This shared signaling complex allowed IL-33 to induce the EGFR-mediated activation of the MAP-kinase signaling pathway and consequently the expression of IL-13. Lack of EGFR expression on T cells abrogated IL-13 expression in infected tissues and impaired host resistance. EGFR expression on Th2 cells was TCR-signaling dependent, and therefore, our data reveal a mechanism by which antigen presentation controls the innate effector function of Th2 cells at the site of inflammation. Mice lacking EGFR expression on T cells are more susceptible to worm infections EGFR forms a complex with T1/ST2, allowing for IL-33 induced IL-13 expression Amphiregulin-mediated EGFR activation is essential for complex formation with T1/ST2 EGFR expression is induced by TCR engagement and sustained by cytokines, such as TSLP At the site of infection, Th2 cells secrete IL-13 upon exposure to IL-33. Minutti et al. now show that TCR-induced expression of the EGFR and its ligand amphiregulin was essential for IL-33-induced IL-13 secretion, revealing a mechanism whereby antigen-specific activation controls the innate effector function of Th2 cells.
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影响因子：
5.4
作者：
Finney, Constance A M;Taylor, Matthew D;Wilson, Mark S;Maizels, Rick M
通讯作者：
Maizels, Rick M
DOI：
10.1126/science.aaj2067
发表时间：
2017-06-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Minutti CM;Jackson-Jones LH;García-Fojeda B;Knipper JA;Sutherland TE;Logan N;Ringqvist E;Guillamat-Prats R;Ferenbach DA;Artigas A;Stamme C;Chroneos ZC;Zaiss DM;Casals C;Allen JE
通讯作者：
Allen JE
影响因子：
4.4
作者：
Liu, F;Whitton, JL
通讯作者：
Whitton, JL
DOI：
10.4049/jimmunol.1502139
发表时间：
2016-03-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Nosbaum A;Prevel N;Truong HA;Mehta P;Ettinger M;Scharschmidt TC;Ali NH;Pauli ML;Abbas AK;Rosenblum MD
通讯作者：
Rosenblum MD
影响因子：
64.8
作者：
通讯作者：
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