TSLP drives acute T(H)2-cell differentiation in lungs.
TSLP drives acute T(H)2-cell differentiation in lungs.
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DOI：
10.1016/j.jaci.2020.03.032
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Ziegler SF
中科院分区：
文献类型：
--
作者：
Lai JF;Thompson LJ;Ziegler SF
胸腺基质淋巴细胞生成素（TSLP）是一种上皮细胞衍生的细胞因子，对粘膜表面2型炎症反应的发展非常重要。在人类中，已经发现TSLP在哮喘患者的肺中升高，并且在小鼠模型中，TSLP可以促进2型气道炎症，主要是通过激活树突状细胞。然而，其作用机制仍不清楚。本研究的目的是提供TSLP介导的2型气道炎症的机制分析。为了剖析TSLP介导的II型应答的机制，用TSLP和抗原处理小鼠以评价细胞免疫应答。流式细胞术分析用于跟踪气道反应，TSLPR的条件性缺失和过继转移用于鉴定参与这种炎症反应的细胞亚群。我们发现TSLP可以直接促进Th 2分化在肺，独立的引流淋巴结。我们还确定了巡逻单核细胞/间质巨噬细胞（CD 11 cIM）的人口，这是必要的和足够的TSLP介导的Th 2分化和气道炎症。Th 2驱动的气道嗜酸性粒细胞增多症通过CD 11 cIM的消融或通过这些细胞中TSLPR信号传导的选择性缺陷而减弱。更重要的是，CD 11 cIM足以诱导肺中的急性Th 2应答，其独立于引流LN中的树突状细胞和T细胞引发。这些发现表明TSLP和CD 11 cIM在急性Th 2依赖性过敏性气道炎症的发展中具有新的机制作用。这项工作还证明了TSLP在促进肺中直接的2型反应中的新作用。我们的研究表明TSLP促进快速的原发性Th 2驱动的气道炎症，这为组织中炎症的发展提供了一种新的机制;更重要的是，抗TSLP治疗在中重度哮喘患者中的疗效提供了潜在的解释。
Thymic stromal lymphopoietin (TSLP) is an epithelial-derived cytokine important for the development of type-2 inflammatory responses at mucosal surfaces. In humans, TSLP has been found to be elevated in the lungs of asthmatics, and in mouse models TSLP can promote type-2 airway inflammation, primarily through the activation of dendritic cells. However, the mechanisms underlying its role remain unclear. The objective of this study is to provide a mechanistic analysis of TSLP-mediated type-2 airway inflammation To dissect the mechanisms of TSLP-mediated type II responses, mice were treated with TSLP and antigen to evaluate cellular immune responses. Flow cytometric analyses were used to follow responses in the airways, and conditional deletion of TSLPR and adoptive transfer were used to identify the cellular subsets involved in this inflammatory response. We show that TSLP can directly promote Th2 differentiation in the lung, independent of the draining lymph node. We also identified a population of patrolling monocytes/interstitial macrophages (CD11cIM) that are both necessary and sufficient for TSLP-mediated Th2 differentiation and airway inflammation. Th2-driven airway eosinophilia is attenuated by ablation of CD11cIM, or by selective deficiency of TSLPR signaling in these cells. More importantly, CD11cIM are sufficient for the induction of acute Th2 responses in the lungs that is independent of dendritic cells and T cell priming in the draining LN. These findings indicate a novel mechanistic role for TSLP and CD11cIM in the development of acute Th2-dependent allergic airway inflammation. This work also demonstrates a new role for TSLP in promoting type-2 responses directly in the lung. Our study showed TSLP promotes rapid primary Th2 driven airway inflammation, which provides a novel mechanism in development of inflammation in tissue; and more importantly, a potential explanation for efficacy of anti-TSLP therapy in moderate-to-severe asthmatic patients.
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影响因子：
30.3
作者：
Hohl TM;Rivera A;Lipuma L;Gallegos A;Shi C;Mack M;Pamer EG
通讯作者：
Pamer EG
DOI：
10.4049/jimmunol.1302175
发表时间：
2013-11-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kitajima M;Ziegler SF
通讯作者：
Ziegler SF
影响因子：
15.9
作者：
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通讯作者：
Ziegler, Steven F.
影响因子：
15.9
作者：
Bedoret, Denis;Wallemacq, Hugues;Bureau, Fabrice
通讯作者：
Bureau, Fabrice
影响因子：
5.3
作者：
Jung, S;Aliberti, J;Littman, DR
通讯作者：
Littman, DR