IL-7受体效应T细胞在原发性干燥综合症患者唇腺中表达增多并与炎性标记物相关
发表者： 竺红(宁夏医学院附属医院)
日期：2015-03-07
浏览次数：128
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摘要(荷兰)：原发性干燥综合征(pSS)患者局部T细胞炎性浸润可导致外分泌腺破坏，临床上引起口干症状。近期有学者报道，pSS患者唇腺组织中白介素-7增高，可诱导增强Th1和Th17活性并促进致炎细胞因子的分泌。白介素-7通过高亲和力的IL-7Rα亚基和γс链发送信号调节其效应。该文献及其他相关文献表明，IL-7R+ CD4 T细胞能够显著增强T细胞受体的活性，而IL-7R-CD4 T细胞无此活性，且其性能是可被调节的。这表明IL-7R+ T细胞参与了PSS患者唇腺组织增强的炎性反应，尤其是与IL-7的表达增高有关。
本研究目的是了解pSS患者与非pSS患者唇腺组织内IL-7受体表达及测定IL-7R+ T细胞的表型特征。运用免疫组化及荧光激活细胞分类术（FACS）研究14例pSS患者及7例非pSS患者唇腺组织中浸润炎性细胞及IL-7R+细胞的表达。与非pSS患者相比，pSS组患者唇腺组织中IL-7R+细胞的数量显著增多(pSS组：244.3±40.7 /mm2；非pSS组：12.3±4.6 /mm2）。IL-7R+ T在受累组织中广泛分布，且集中分布在富含CD-3淋巴细胞的区域。IL-7R+ T细胞与唇腺组织局部病变参数及炎细胞浸润显著相关（P＜0.01，淋巴细胞灶评分（lymphocytic focus score ，LFS); r=0.744 ， IgA+ 细胞 r=−0.658，CD3 r=0.890; CD20 r=0.717; CD1a r=0.660; CD208 r=0.763）。
通过FACS法对两组原发性干燥综合症患者唇腺组织分离细胞的分析证实，pSS组CD3 和 IL-7R+ CD3 T细胞所占百分比均显著增高（P＜0.01）。此外，研究发现IL-7R在多数的CD4淋巴细胞（平均66% ± 5%）和CD8淋巴细胞（平均56% ± 4%）中足量表达，而在其他CD45+白细胞及CD45−组织细胞中不表达或极少表达。IL-7R+ CD3、CD4和CD8 T细胞与LFS存在显著的相关性（相应p及r值依次为；p≤0.05, r=0.533; p≤0.01, r=0.593; p≤0.01, r=0.631）。
pSS患者唇腺组织中与腺体炎症相关的IL-7R+ T 细胞过量表达，表明表达升高的白介素-7能够通过激活白细胞介素-7受体效应T细胞参与腺体的炎性反应。因此，阻断IL-7受体或许是治疗pSS的一条新策略。
附原文： Abstract In patients with pSS local T cell-driven inflammation contributes to destruction of exocrine glands associated with clinical symptoms of dryness. Recently the authors documented increased interleukin (IL)-7 in labial salivary glands (LSG) of pSS patients that was capable to induce Th1 and Th17 activity and proinflammatory cytokine secretion. IL-7 mediates its effects by signaling through the high affinity IL-7Rα subunit and γc chain. The authors and others have shown that IL-7R+ CD4 T cells that strongly proliferate upon TCR activation, while IL-7R− CD4 T cells are anergic and can be regulatory of nature. This suggests that IL-7R+ T cells contribute to the increased inflammatory response in LSG of pSS patients, especially in the presence of increased local IL-7 expression. To identify IL-7R expression in the labial salivary gland and to examine the phenotypical characteristics of IL-7R+ T cells between pSS and non-Sjögren's syndrome sicca (nSS) patients. The presence of infiltrating immune cells and IL-7R+ cells in inflamed salivary glands of pSS patients (n=14) and non-inflamed LSG of nSS patients (n=7) was studied by immunohistochemistry and FACS analysis upon tissue digestion. In the LSG of pSS patients significantly increased numbers of IL-7R+ cells were found as compared to nSS (pSS vs nSS; 244.3±40.7 vs 12.3±4.6 cells/mm2). IL7R+ T cells were found throughout the tissue but mainly in the CD3-rich lymphocytic areas. IL7R+ T cells significantly (all p<0.01) correlated with local disease parameters (lymphocytic focus score (LFS); r=0.744 and % IgA+ cells r=−0.658) as well as with immune cells present in the LSG (CD3 r=0.890; CD20 r=0.717; CD1a r=0.660; CD208 r=0.763). FACS analysis of isolated cells from patients' LSG confirmed a strongly increased percentage of both CD3 and IL-7R+ CD3 T cells in pSS as compared to nSS (both p<0.01). Furthermore, abundant IL-7R expression was detected on high proportions of CD4 and CD8 (on average 66% ± 5% and 56% ± 4%, respectively). Other CD45+ leucocytes and CD45− tissue cells did not or hardly express the IL-7R. IL-7R+ CD3, CD4 and CD8 T cells as percentage of the total LSG cells significantly correlated with the LFS (p≤0.05, r=0.533; p≤0.01, r=0.593; p≤0.01, r=0.631, respectively). The abundant presence of IL-7R+ T cells in the inflamed salivary glands of pSS patients, which correlates to inflammation, suggests that increased IL-7 expression could significantly contribute to glandular inflammation by activation of IL-7R+ effector T cells. Hence, blockade of the IL-7R might be a novel therapeutic strategy for pSS.
引自：A Bikker,AA Kruize,M Wenting,et al . IL-7 receptor effector T cells are increased in the inflamed salivary glands of pSS patients and correlate with inflammatory markers . Ann Rheum Dis 2011;70:A51 doi:10.1136/ard.2010.148981.22 （注：干燥综合症病人或亲属可加QQ群交流，群号： 118194945 ，本网站站长私人微信号： ssgzz88 ）
本研究目的是了解pSS患者与非pSS患者唇腺组织内IL-7受体表达及测定IL-7R+ T细胞的表型特征。运用免疫组化及荧光激活细胞分类术（FACS）研究14例pSS患者及7例非pSS患者唇腺组织中浸润炎性细胞及IL-7R+细胞的表达。与非pSS患者相比，pSS组患者唇腺组织中IL-7R+细胞的数量显著增多(pSS组：244.3±40.7 /mm2；非pSS组：12.3±4.6 /mm2）。IL-7R+ T在受累组织中广泛分布，且集中分布在富含CD-3淋巴细胞的区域。IL-7R+ T细胞与唇腺组织局部病变参数及炎细胞浸润显著相关（P＜0.01，淋巴细胞灶评分（lymphocytic focus score ，LFS); r=0.744 ， IgA+ 细胞 r=−0.658，CD3 r=0.890; CD20 r=0.717; CD1a r=0.660; CD208 r=0.763）。
通过FACS法对两组原发性干燥综合症患者唇腺组织分离细胞的分析证实，pSS组CD3 和 IL-7R+ CD3 T细胞所占百分比均显著增高（P＜0.01）。此外，研究发现IL-7R在多数的CD4淋巴细胞（平均66% ± 5%）和CD8淋巴细胞（平均56% ± 4%）中足量表达，而在其他CD45+白细胞及CD45−组织细胞中不表达或极少表达。IL-7R+ CD3、CD4和CD8 T细胞与LFS存在显著的相关性（相应p及r值依次为；p≤0.05, r=0.533; p≤0.01, r=0.593; p≤0.01, r=0.631）。
pSS患者唇腺组织中与腺体炎症相关的IL-7R+ T 细胞过量表达，表明表达升高的白介素-7能够通过激活白细胞介素-7受体效应T细胞参与腺体的炎性反应。因此，阻断IL-7受体或许是治疗pSS的一条新策略。
附原文： Abstract In patients with pSS local T cell-driven inflammation contributes to destruction of exocrine glands associated with clinical symptoms of dryness. Recently the authors documented increased interleukin (IL)-7 in labial salivary glands (LSG) of pSS patients that was capable to induce Th1 and Th17 activity and proinflammatory cytokine secretion. IL-7 mediates its effects by signaling through the high affinity IL-7Rα subunit and γc chain. The authors and others have shown that IL-7R+ CD4 T cells that strongly proliferate upon TCR activation, while IL-7R− CD4 T cells are anergic and can be regulatory of nature. This suggests that IL-7R+ T cells contribute to the increased inflammatory response in LSG of pSS patients, especially in the presence of increased local IL-7 expression. To identify IL-7R expression in the labial salivary gland and to examine the phenotypical characteristics of IL-7R+ T cells between pSS and non-Sjögren's syndrome sicca (nSS) patients. The presence of infiltrating immune cells and IL-7R+ cells in inflamed salivary glands of pSS patients (n=14) and non-inflamed LSG of nSS patients (n=7) was studied by immunohistochemistry and FACS analysis upon tissue digestion. In the LSG of pSS patients significantly increased numbers of IL-7R+ cells were found as compared to nSS (pSS vs nSS; 244.3±40.7 vs 12.3±4.6 cells/mm2). IL7R+ T cells were found throughout the tissue but mainly in the CD3-rich lymphocytic areas. IL7R+ T cells significantly (all p<0.01) correlated with local disease parameters (lymphocytic focus score (LFS); r=0.744 and % IgA+ cells r=−0.658) as well as with immune cells present in the LSG (CD3 r=0.890; CD20 r=0.717; CD1a r=0.660; CD208 r=0.763). FACS analysis of isolated cells from patients' LSG confirmed a strongly increased percentage of both CD3 and IL-7R+ CD3 T cells in pSS as compared to nSS (both p<0.01). Furthermore, abundant IL-7R expression was detected on high proportions of CD4 and CD8 (on average 66% ± 5% and 56% ± 4%, respectively). Other CD45+ leucocytes and CD45− tissue cells did not or hardly express the IL-7R. IL-7R+ CD3, CD4 and CD8 T cells as percentage of the total LSG cells significantly correlated with the LFS (p≤0.05, r=0.533; p≤0.01, r=0.593; p≤0.01, r=0.631, respectively). The abundant presence of IL-7R+ T cells in the inflamed salivary glands of pSS patients, which correlates to inflammation, suggests that increased IL-7 expression could significantly contribute to glandular inflammation by activation of IL-7R+ effector T cells. Hence, blockade of the IL-7R might be a novel therapeutic strategy for pSS.
引自：A Bikker,AA Kruize,M Wenting,et al . IL-7 receptor effector T cells are increased in the inflamed salivary glands of pSS patients and correlate with inflammatory markers . Ann Rheum Dis 2011;70:A51 doi:10.1136/ard.2010.148981.22 （注：干燥综合症病人或亲属可加QQ群交流，群号： 118194945 ，本网站站长私人微信号： ssgzz88 ）