Thymic stromal lymphopoietin, OX40-ligand, and interleukin-25 in allergic responses.
Thymic stromal lymphopoietin, OX40-ligand, and interleukin-25 in allergic responses.
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DOI：
10.1111/j.1365-2222.2009.03241.x
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发表时间：
2009-06
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;Liu YJ
过敏性疾病通常由环境过敏原引发，其诱导显性2型免疫应答，其特征在于浸润的TH 2淋巴细胞、嗜酸性粒细胞和升高的TH 2细胞因子。除了TH 2型免疫应答外，还经常观察到与组织重塑相关的上皮应激和损伤，这表明上皮细胞可能在调节过敏反应中起重要作用。树突状细胞（Dendritic cells，DCs）是一种专职抗原提呈细胞，具有采集变应原的功能，被认为是指导TH 2免疫应答的关键细胞。炎症上皮是否可以调节先天免疫，如巨噬细胞和DC，这反过来又指导适应性免疫一直是假设。胸腺基质淋巴细胞生成素（thymic stromal lymphopoietin，TSLP）是一种上皮细胞源性细胞因子，能强烈激活DCs，其研究为上皮屏障通过调节免疫反应引发变态反应性疾病提供了重要证据。OX 40/OX 40 L相互作用是负责TSLP激活的DC诱导和维持TH 2应答的分子触发物的发现为TSLP介导的变态反应提供了合理的分子解释。在表征促炎性IL-17细胞因子家族方面的最新进展增加了过敏性炎症调节的额外复杂性。TSLP-DC可以诱导TH 2记忆细胞的稳健扩增并通过上调其IL-17 RB（IL-25 R）的表面表达来增强功能属性，IL-17 RB（IL-25 R）是细胞因子IL-17 E（IL-25）的受体，IL-17 E（IL-25）是IL-17细胞因子家族的不同成员。由上皮细胞和其他先天细胞（例如嗜酸性粒细胞、嗜碱性粒细胞和肥大细胞）产生的IL-17 E（也称为IL-25）显示通过增强TH 2细胞因子产生来调节适应性免疫。这些令人兴奋的发现扩展了我们对导致过敏性炎症的复杂免疫级联反应的认识，并可能为过敏性疾病的治疗提供新的治疗方法。
Allergic diseases are often triggered by environmental allergens that induce dominant type2 immune responses, characterized by the infiltrated TH2 lymphocytes, eosinophils, and elevated TH2 cytokines. In addition to TH2 type immune responses, epithelial stress and injury linked to tissue remodelling are often observed, suggesting that epithelial cells may play important role in regulating allergic responses. Dendritic cells (DCs), the professional antigen-presenting cells with the capabilities of sampling allergens, are considered as the key player on instructing TH2 immune responses. Whether inflamed epithelium can regulate innate immunity, such as macrophages and DCs, which in turns instruct adaptive immunity has long been hypothesized. Studies of TSLP (thymic stromal lymphopoietin), an epithelial cells-derived cytokine, that can strongly activate DCs, provide important evidences that the epithelial barrier can trigger allergic diseases by regulating immune responses. The finding that OX40/OX40L interactions are the molecular trigger responsible for the induction and maintenance of TH2 responses by TSLP-activated DCs provides a plausible molecular explanation for TSLP-mediated allergy. Recent progresses in characterizing the proinflammatory IL-17 cytokine family have added an additional layer of complexity on the regulation of allergic inflammation. TSLP-DCs can induce a robust expansion of TH2 memory cells and strengthen functional attributes by upregulating their surface expression of IL-17RB (IL-25R), the receptor for cytokine IL-17E (IL-25), a distinct member of IL-17 cytokine family. IL-17E (also know as IL-25) produced by epithelial cells, and other innate cells, such as eosinphils, basophils, and mast cells, are shown to regulate adaptive immunity by enhancing TH2 cytokine productions. These exciting findings expand our knowledge of the complex immunological cascades that result in allergic inflammation and may provide novel therapeutic approaches for the treatments of allergic diseases.
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鉴定人OX-40配体，这是具有与肿瘤坏死因子同源的CD4+ T细胞的costimulator。
影响因子：
15.3
作者：
Godfrey, Wayne R.;Fagnoni, Francesco F.;Haraa, Marwan A.;Buck, David;Engleman, Edgar G.
通讯作者：
Engleman, Edgar G.
影响因子：
5.4
作者：
Hoshino, A;Tanaka, Y;Okumura, K
通讯作者：
Okumura, K
DOI：
10.1073/pnas.0507385102
发表时间：
2005-10-11
影响因子：
11.1
作者：
Li, M;Messaddeq, N;Chambon, P
通讯作者：
Chambon, P
影响因子：
4.8
作者：
Chen, Y;Thai, P;Wu, R
通讯作者：
Wu, R
影响因子：
4.4
作者：
Kato, Atsushi;Favoreto, Silvio, Jr.;Schleimer, Robert P.
通讯作者：
Schleimer, Robert P.