Lymphotoxin controls the IL-22 protection pathway in gut innate lymphoid cells during mucosal pathogen challenge.
Lymphotoxin controls the IL-22 protection pathway in gut innate lymphoid cells during mucosal pathogen challenge.
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DOI：
10.1016/j.chom.2011.06.002
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发表时间：
2011-07-21
影响因子：
30.3
通讯作者：
Fu YX
中科院分区：
文献类型：
--
作者：
Tumanov AV;Koroleva EP;Guo X;Wang Y;Kruglov A;Nedospasov S;Fu YX
先天性淋巴样细胞（ILC）已成为调节粘膜表面保护性免疫和免疫病理学之间平衡的重要参与者。然而，在粘膜致病性攻击过程中调节ILC效应子功能的机制尚不清楚。使用感染了天然小鼠肠道病原体啮齿类柠檬酸杆菌的小鼠，我们证明了光毒素（LT）对肠道ILC产生IL-22是必不可少的。阻断LTβR信号通路可显著降低C.啮齿类感染相反，刺激LTβR信号转导诱导LT缺陷小鼠中的IL-22保护途径。此外，外源性IL-22表达可拯救LTβR缺陷小鼠。产生IL-22的ILC主要位于结肠的淋巴滤泡中，并且与树突状细胞密切相互作用。最后，我们发现LT驱动的正反馈环通过树突状细胞中的LTβR信号控制RORγt+ ILC产生IL-22。总之，我们发现肠淋巴滤泡中的LTβR信号调节ILC对粘膜病原体攻击的反应中IL-22的产生。
Innate lymphoid cells (ILCs) have emerged as important players regulating the balance between protective immunity and immunopathology at mucosal surfaces. However, mechanisms that regulate ILCs effector functions during mucosal pathogenic challenge are poorly defined. Using mice infected with the natural mouse enteric pathogen Citrobacter rodentium, we demonstrate that lymphotoxin (LT) is essential for IL-22 production by intestinal ILCs. Blocking of LTβR signaling dramatically reduced intestinal IL-22 production after C. rodentium infection. Conversely, stimulating LTβR signaling induced IL-22 protection pathway in LT-deficient mice. Furthermore, exogenous IL-22 expression rescued LTβR deficient mice. IL-22 producing ILCs were predominantly located in lymphoid follicles in the colon, and interacted closely with dendritic cells. Finally, we find that an LT-driven positive feedback loop controls IL-22 production by RORγt+ ILCs via LTβR signaling in dendritic cells. Altogether, we show that LTβR signaling in gut lymphoid follicles regulates IL-22 production by ILCs in response to mucosal pathogen challenge.
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影响因子：
32.4
作者：
Sonnenberg GF;Monticelli LA;Elloso MM;Fouser LA;Artis D
通讯作者：
Artis D
影响因子：
64.8
作者：
Cella, Marina;Fuchs, Anja;Vermi, William;Facchetti, Fabio;Otero, Karel;Lennerz, Jochen K. M.;Doherty, Jason M.;Mills, Jason C.;Colonna, Marco
通讯作者：
Colonna, Marco
DOI：
10.1084/jem.20100052
发表时间：
2011-01-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lochner M;Ohnmacht C;Presley L;Bruhns P;Si-Tahar M;Sawa S;Eberl G
通讯作者：
Eberl G
影响因子：
32.4
作者：
Kabashima, K;Banks, TA;Cyster, JG
通讯作者：
Cyster, JG
影响因子：
30.5
作者：
通讯作者：
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