IL-17-producing ST2(+) group 2 innate lymphoid cells play a pathogenic role in lung inflammation.
IL-17-producing ST2(+) group 2 innate lymphoid cells play a pathogenic role in lung inflammation.
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产生 IL-17 ST2( ) 2 组先天淋巴细胞在肺部炎症中发挥致病作用
DOI：
10.1016/j.jaci.2018.03.007
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发表时间：
2019-01
期刊：
影响因子：
--
通讯作者：
Qiu J
中科院分区：
文献类型：
--
作者：
Cai T;Qiu J;Ji Y;Li W;Ding Z;Suo C;Chang J;Wang J;He R;Qian Y;Guo X;Zhou L;Sheng H;Shen L;Qiu J
IL-17在哮喘中起致病作用。由IL-25驱动的ST 2 − iILC 2s（炎性第2组先天淋巴细胞）可以产生IL-17，而ST 2 + nILC 2s（天然ILC 2s）产生很少的IL-17。我们表征了肺炎症过程中的ST 2 +IL-17+ ILC 2s，并确定了ST 2 +IL-17+ ILC 2s的发病机制和分子调控。通过木瓜蛋白酶或IL-33诱导肺部炎症。通过流式细胞术检查来自野生型、Rag 1 − /−、Rorcgfp/gfp和Ahr−/−小鼠的肺ILC 2的IL-17产生。进行骨髓转移实验以评估造血MyD 88信号传导在调节ILC 2产生IL-17中的作用。在用IL-33、白三烯和NFAT、p38、JNK或NF-κB的抑制剂处理的纯化的幼稚ILC 2中分析IL-17的mRNA表达。IL-17+ ILC 2的发病机制通过将野生型或IL 17 −/− ILC 2转移到Rag 2 −/− IL 2 rg −/−小鼠中来确定，这些小鼠进一步诱导肺部炎症。最后，在ST 2 +IL-17+ ILC 2和ST 2 +IL-17− ILC 2之间比较了106个ILC 2标签基因的表达。木瓜蛋白酶或IL-33处理促进了ST 2 + ILC 2（我们称为ILC 217）的IL-17产生，但不是ST 2 − ILC 2。Ahr而不是RORγt促进ILC 217产生IL-17。MyD 88信号传导的造血区室对于ILC 217的诱导是必需的。IL-33与通过NFAT激活发出信号的白三烯协同作用，以促进ILC 217中的IL-17。IL 17 −/− ILC 2在肺部炎症中的致病性较低。ILC 217同时表达IL-5和IL-13，但几乎不表达GM-CSF。在肺部炎症期间，IL-33和白三烯协同诱导ILC 217。ILC 217是肺部炎症中IL-17的高致病性和意想不到的来源。
IL-17 plays a pathogenic role in asthma. ST2− iILC2s (inflammatory group 2 innate lymphoid cells) driven by IL-25 can produce IL-17, while ST2+nILC2s (natural ILC2s) produce few IL-17. We characterized the ST2+IL-17+ILC2s during lung inflammation and determined the pathogenesis and molecular regulation of ST2+IL-17+ILC2s. Lung inflammation was induced by papain or IL-33. IL-17 production by lung ILC2s from wild-type, Rag1− /−, Rorcgfp/gfp and Ahr−/− mice was examined by flow cytometry. Bone marrow transfer experiment was performed to evaluate hematopoietic MyD88 signaling in regulating IL-17 production by ILC2s. mRNA expression of IL-17 was analyzed in purified naïve ILC2s treated with IL-33, leukotrienes and inhibitors for NFAT, p38, JNK or NF-κB. The pathogenesis of IL-17+ILC2s was determined by transferring wild-type or Il17−/−ILC2s to Rag2−/−Il2rg−/− mice which were further induced lung inflammation. Finally, the expression of 106 ILC2 signature genes was compared between ST2+IL-17+ILC2s and ST2+IL-17−ILC2s. Papain or IL-33 treatment boosted IL-17 production from ST2+ILC2s (referred to by us as ILC217s), but not ST2−ILC2s. Ahr, but not RORγt, facilitated the production of IL-17 by ILC217s. Hematopoietic compartment of MyD88 signaling is essential for the induction of ILC217s. IL-33 works in synergy with leukotrienes, which signal through NFAT activation, to promote IL-17 in ILC217s. Il17−/− ILC2s were less pathogenic in lung inflammation. ILC217s concomitantly expressed IL-5 and IL-13 but expressed few GM-CSF. During lung inflammation, IL-33 and leukotrienes synergistically induce ILC217s. ILC217s are highly pathogenic and unexpected source for IL-17 in lung inflammation.
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影响因子：
64.8
作者：
Esplugues, Enric;Huber, Samuel;Gagliani, Nicola;Hauser, Anja E.;Town, Terrence;Wan, Yisong Y.;O'Connor, William, Jr.;Rongvaux, Anthony;Van Rooijen, Nico;Haberman, Ann M.;Iwakura, Yoichiro;Kuchroo, Vijay K.;Kolls, Jay K.;Bluestone, Jeffrey A.;Herold, Kevan C.;Flavell, Richard A.
通讯作者：
Flavell, Richard A.
影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
14.2
作者：
Kim, Hye Young;Chang, Ya-Jen;Chuang, Ya-Ting;Lee, Hyun-Hee;Kasahara, David I.;Martin, Thomas;Hsu, Joyce T.;Savage, Paul B.;Shore, Stephanie A.;Freeman, Gordon J.;DeKruyff, Rosemarie H.;Umetsu, Dale T.
通讯作者：
Umetsu, Dale T.
影响因子：
32.4
作者：
Halim, Timotheus Y. F.;Krauss, Ramona H.;Takei, Fumio
通讯作者：
Takei, Fumio
影响因子：
14.2
作者：
Barlow, Jillian L.;Bellosi, Agustin;McKenzie, Andrew N. J.
通讯作者：
McKenzie, Andrew N. J.