IL-25 augments type 2 immune responses by enhancing the expansion and functions of TSLP-DC-activated Th2 memory cells.
IL-25 augments type 2 immune responses by enhancing the expansion and functions of TSLP-DC-activated Th2 memory cells.
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DOI：
10.1084/jem.20070406
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发表时间：
2007-08-06
期刊：
影响因子：
--
通讯作者：
Liu YJ
中科院分区：
文献类型：
--
作者：
Wang YH;Angkasekwinai P;Lu N;Voo KS;Arima K;Hanabuchi S;Hippe A;Corrigan CJ;Dong C;Homey B;Yao Z;Ying S;Huston DP;Liu YJ
白细胞介素（IL）25（IL-17 E）是IL-17细胞因子家族的一个独特成员，在引起以嗜酸性粒细胞和Th 2记忆细胞浸润为特征的辅助性T细胞2型（Th 2）细胞介导的炎症中起重要作用。然而，细胞来源，靶细胞和潜在机制在人类中仍然难以捉摸。我们证明，表达不同水平IL-25受体（R）的人Th 2记忆细胞是响应细胞类型之一。当Th 2中枢记忆细胞被胸腺基质淋巴细胞生成素（TSLP）激活的树突状细胞（DC）、稳态细胞因子或用于抗原触发的T细胞受体刺激时，IL-25促进细胞扩增和Th 2细胞因子产生。IL-25诱导的Th 2记忆细胞功能增强与加塔-3、c-MAF和JunB以IL-4非依赖性方式持续表达相关。尽管角质形成细胞、肥大细胞、嗜酸性粒细胞和嗜碱性粒细胞表达IL-25转录本，但发现正常和特应性受试者的活化嗜酸性粒细胞和嗜碱性粒细胞分泌具有生物活性的IL-25蛋白，从而增强Th 2记忆细胞的功能。在哮喘肺组织和特应性皮炎皮肤病变中观察到IL-25和IL-25 R转录物的表达升高，将其可能的作用与过敏性疾病的加重联系起来。我们的研究结果提供了一个合理的解释，IL-25产生的先天效应嗜酸性粒细胞和嗜碱性粒细胞可能会增加过敏性炎症，通过增强适应性Th 2记忆细胞的维护和功能。
Interleukin (IL) 25 (IL-17E), a distinct member of the IL-17 cytokine family, plays important roles in evoking T helper type 2 (Th2) cell–mediated inflammation that features the infiltrations of eosinophils and Th2 memory cells. However, the cellular sources, target cells, and underlying mechanisms remain elusive in humans. We demonstrate that human Th2 memory cells expressing distinctive levels of IL-25 receptor (R) are one of the responding cell types. IL-25 promotes cell expansion and Th2 cytokine production when Th2 central memory cells are stimulated with thymic stromal lymphopoietin (TSLP)–activated dendritic cells (DCs), homeostatic cytokines, or T cell receptor for antigen triggering. The enhanced functions of Th2 memory cells induced by IL-25 are associated with sustained expression of GATA-3, c-MAF, and JunB in an IL-4–independent manner. Although keratinocytes, mast cells, eosinophils, and basophils express IL-25 transcripts, activated eosinophils and basophils from normal and atopic subjects were found to secrete bioactive IL-25 protein, which augments the functions of Th2 memory cells. Elevated expression of IL-25 and IL-25R transcripts was observed in asthmatic lung tissues and atopic dermatitis skin lesions, linking their possible roles with exacerbated allergic disorders. Our results provide a plausible explanation that IL-25 produced by innate effector eosinophils and basophils may augment the allergic inflammation by enhancing the maintenance and functions of adaptive Th2 memory cells.
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影响因子：
14.2
作者：
Bressler, RB;Lesko, J;Huston, DP
通讯作者：
Huston, DP
影响因子：
4.4
作者：
Odemuyiwa, SO;Ghahary, A;Moqbel, R
通讯作者：
Moqbel, R
影响因子：
4.4
作者：
Reche, PA;Soumelis, V;Bazan, JF
通讯作者：
Bazan, JF
影响因子：
30.5
作者：
Watanabe, N;Hanabuchi, S;Liu, YJ
通讯作者：
Liu, YJ
DOI：
10.1084/jem.20051745
发表时间：
2006-02-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Liu YJ
通讯作者：
Liu YJ