Agostini Carlo, Cabrelle Anna, Calabrese Fiorella, Bortoli Michela, Scquizzato Elisa, Carraro Samuela, Miorin Marta, Beghè Bianca, Trentin Livio, Zambello Renato, Facco Monica, Semenzato Gianpietro
Department of Clinical Medicine, Clinical Immunology Branch, Division of Pneumology and Institute of Pathology, Padua University School of Medicine, Italy.
Am J Respir Crit Care Med. 2005 Nov 15;172(10):1290-8. doi: 10.1164/rccm.200501-142OC. Epub 2005 Aug 11.
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.
The evaluation of the role of Bonzo/CXCR6 and its ligand CXCL16 in the pathogenesis of sarcoidosis.
Immunocompetent cells infiltrating sarcoid lung have been evaluated by flow cytometry, confocal microscopy, immunohistochemical and molecular analysis, and functional assays.
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.
T cells coexpressing CXCR3 and CXCR6 act coordinately with respective ligands and Th1 inflammatory cytokines in the alveolitic/granuloma phases of the disease.
受体表达决定了趋化因子对免疫活性细胞的作用范围。我们之前已经表明，趋化因子受体CXCR3在结节病患者肺部浸润的1型辅助性T细胞（Th1）中高度表达。
评估Bonzo/CXCR6及其配体CXCL16在结节病发病机制中的作用。
通过流式细胞术、共聚焦显微镜、免疫组织化学和分子分析以及功能测定，对浸润结节病肺部的免疫活性细胞进行了评估。
从结节病患者支气管肺泡灌洗中分离出的Th1细胞和肺泡炎T细胞共表达CXCR3和CXCR6。肺标本的免疫组织化学分析表明，CXCR6+ T细胞浸润到肉芽肿中央核心周围的肺间质中。结节病组织浸润的巨噬细胞和/或形成肉芽肿核心的巨噬细胞大量表达CXCR6配体CXCL16。从功能角度来看，在迁移试验中，结节病Th1细胞能够对CXCL10和CXCL16作出反应。体外动力学研究表明，虽然CXCR3可被白细胞介素（IL）-15和IL-18快速诱导，但CXCR6的诱导较慢（8天），且主要受IL-15调节。
共表达CXCR3和CXCR6的T细胞在疾病的肺泡炎/肉芽肿阶段与各自的配体和Th1炎症细胞因子协同发挥作用。
