Role for CXCR6 and its ligand CXCL16 in the pathogenesis of T-cell alveolitis in sarcoidosis
Role for CXCR6 and its ligand CXCL16 in the pathogenesis of T-cell alveolitis in sarcoidosis
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DOI：
10.1164/rccm.200501-142oc
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发表时间：
2005-11-15
影响因子：
24.7
通讯作者：
Semenzato, G
中科院分区：
文献类型：
--
作者：
Agostini, C;Cabrelle, A;Semenzato, G
原理：受体表达决定了趋化因子对免疫活性细胞的作用谱。我们以前已经表明趋化因子受体CXCR 3是高度表达的T辅助1型（Th 1）细胞浸润的结节病患者的肺。目的：评价Bonzo/CXCR 6及其配体CXCL 16在结节病发病机制中的作用。方法：免疫活性细胞浸润结节病肺已通过流式细胞术，共聚焦显微镜，免疫组化和分子分析，和功能测定。主要结果：从结节病和T细胞肺泡炎患者的支气管肺泡灌洗中分离的Th 1细胞共表达CXCR 3和CXCR 6。肺标本的免疫组织化学分析显示CXCR 6（+）T细胞浸润肉芽肿中心周围的肺间质。CXCR 6配体CXCL 16在浸润类肉瘤组织和/或形成肉芽肿核心的巨噬细胞中大量表达。从功能的角度来看，类肉瘤Th 1细胞能够在迁移试验中对CXCL 10和CXCL 16产生应答。体外动力学研究表明，IL-15和IL-18可快速诱导CXCR 3的表达，而CXCR 6的诱导则缓慢（8d），主要受IL-15的调节。结论：在肺泡/肉芽肿期，共表达CXCR 3和CXCR 6的T细胞与各自的配体和Th 1型炎性细胞因子协同作用。
Rationale: Receptor expression dictates the spectrum of chemokine actions on immunocompetent cells. We have previously shown that the chemokine receptor CXCR3 is highly expressed by T-helper type 1 (Th1) cells infiltrating the lungs of patients with sarcoidosis.Objectives:The evaluation of the role of Bonzo/CXCR6 and its ligand CXCL16 in the pathogenesis of sarcoidosis.Methods: Immunocompetent cells infiltrating sarcoid lung have been evaluated by flow cytometry, confocal microscopy, immunohistochemical and molecular analysis, and functional assays.Main Results: Th1 cells isolated from the bronchoalveolar lavage of patients with sarcoidosis and T-cell alveolitis coexpressed CXCR3 and CXCR6. Immunohistochemical analysis of lung specimens has shown that CXCR6(+) T cells infiltrated lung interstitium surrounding the central core of the granuloma. The CXCR6 ligand CXCL16 was abundantly expressed by macrophages infiltrating sarcoid tissue and/or forming the granuloma core. From a functional point of view, sarcoid Th1 cells were able to respond to CXCL10 and CXCL16 in migratory assay. In vitro kinetic studies demonstrated that, although CXCR3 was rapidly induced by interleukin (IL)-15 and IL-18, CXCR6 induction was slow (8 d) and mainly regulated by IL-15.Conclusions: T cells coexpressing CXCR3 and CXCR6 act coordinately with respective ligands and Th1 inflammatory cytokines in the alveolitic/granuloma phases of the disease.