Expanded lung T-bet+RORγT+ CD4+ T-cells in sarcoidosis patients with a favourable disease phenotype
Expanded lung T-bet+RORγT+ CD4+ T-cells in sarcoidosis patients with a favourable disease phenotype
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DOI：
10.1183/13993003.00092-2016
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发表时间：
2016-08-01
影响因子：
24.3
通讯作者：
Grunewald, Johan
中科院分区：
文献类型：
--
作者：
Kaiser, Ylva;Lepzien, Rico;Grunewald, Johan
肺结节病的疾病表型是由临床而不是免疫标准来区分的。我们的目的是表征CD4(+) t细胞谱系可塑性的模式，这是急性形式、Lofgren综合征和异质性、潜在进行性“非Lofgren”形式之间临床表现和病程差异的基础。33例肺结节病患者和9例对照组行支气管镜检查并支气管肺泡灌洗。利用流式细胞术和多色荧光斑点技术评估灌洗液和外周血中CD4(+) t细胞转录因子、趋化因子受体和t细胞受体的表达、增殖和细胞因子的产生。CD4(+) T细胞同时表达辅助性T细胞（Th）1和Th17转录调节因子T-bet和ROR γ T （T-bet(+)ROR γ T+）在所有受试者的灌洗液中被鉴定出来，但在血液中没有，并且在Lofgren患者中明显更高。T-bet(+)ROR γ T+细胞增殖活跃，产生干扰素(IFN) γ和白细胞介素(IL)-17A，共表达趋化因子受体CXCR3和CCR6，并与非慢性疾病相关。T细胞受体限制性V α 2.3(+)V β 22(+) T细胞强烈共表达T-bet/ROR γ T和CXCR3/CCR6。细胞因子的产生在Lofgren患者中更为异质性，IL-17A、IL-10、IL-22和IL-2显著升高，但IFN γ降低。在这里，我们证明了肺T-bet(+)ROR γ T(+)CXCR3(+)CCR6(+) CD4(+) T细胞和th17相关细胞因子的存在，特别是在预后良好的结节病患者中，表明肺中存在Th1/ th17许可环境，对疾病的缓解有影响。
Disease phenotypes of pulmonary sarcoidosis are distinguished by clinical rather than immunological criteria. We aimed to characterise patterns of CD4(+) T-cell lineage plasticity underlying the differences in clinical presentation and disease course between the acute form, Lofgren's syndrome, and the heterogeneous, potentially progressive "non-Lofgren" form.33 pulmonary sarcoidosis patients and nine controls underwent bronchoscopy with bronchoalveolar lavage. CD4(+) T-cell transcription factor, chemokine receptor and T-cell receptor expression, proliferation and cytokine production were assessed in the lavage fluid and peripheral blood using flow cytometry and multicolour FluoroSpot.CD4(+) T-cells simultaneously expressing the T-helper cell (Th)1 and Th17 transcriptional regulators T-bet and ROR gamma T (T-bet(+)ROR gamma T+) were identified in the lavage, but not blood, of all subjects, and to a significantly higher degree in Lofgren's patients. T-bet(+)ROR gamma T+ cells proliferated actively, produced interferon (IFN)gamma and interleukin (IL)-17A, co-expressed the chemokine receptors CXCR3 and CCR6, and correlated with nonchronic disease. T-cell receptor-restricted V alpha 2.3(+)V beta 22(+) T-cells strongly co-expressed T-bet/ROR gamma T and CXCR3/CCR6. Cytokine production was more heterogeneous in Lofgren's patients, with significantly higher IL-17A, IL-10, IL-22 and IL-2, but lower IFN gamma.Here we demonstrate the presence of lung T-bet(+)ROR gamma T(+)CXCR3(+)CCR6(+) CD4(+) T-cells and Th17-associated cytokines especially in sarcoidosis patients with a favourable prognosis, suggesting a Th1/Th17-permissive environment in the lung with implications for disease resolution.