Involvement of CD161+Vδ1+γδT cells in systemic sclerosis: association with interstitial pneumonia
Involvement of CD161+Vδ1+γδT cells in systemic sclerosis: association with interstitial pneumonia
复制标题
CD161+Vδ1+γδT 细胞参与系统性硬化症：与间质性肺炎的关联
DOI：
10.1093/rheumatology/keu246
复制
发表时间：
2014
期刊：
影响因子：
5.5
通讯作者：
Sumida T
中科院分区：
文献类型：
--
作者：
Segawa S;Goto D;Horikoshi M;Kondo Y;Umeda N;Hagiwara S;Yokosawa M;Hirota T;Miki H;Tsuboi H;Ogishima H;Suzuki T;Matumoto I;Sumida T
目的：间质性肺炎（IP）是一种慢性进行性间质性肺疾病，死亡率高，预后差。然而，IP的发病机制仍有待阐明。本研究旨在阐明CD161+Vδ1+γδT细胞在SSc IP患者中的作用。方法测定外周血单核细胞（PBMC）中CD161+Vδ1+γδT细胞的比例和血清唾液酸化糖抗原（KL-6）水平。使用 CD161− 和 CD161+Vδ1+γδ T 细胞进行基因芯片分析。检测CD161+Vδ1+γδT细胞的细胞因子和趋化因子表达，并用于评估培养上清液对成纤维细胞增殖的影响。结果。SSc中CD161+Vδ1+γδT细胞的比例显着高于健康对照（HC），且与IP阳性SSc患者血清KL-6水平呈负相关。 CD161+Vδ1+γδ T 细胞中趋化因子配体 3 (CCL3) 的基因和 mRNA 表达水平显着高于 CD161−Vδ1+γδ T 细胞。 IP 阳性 SSc 患者中的 CD161+Vδ1+γδ T 细胞显示出比 HC 中更高的 CCL3 产量和更低的 IFN-γ 产量。 IP阴性和IP阳性SSc患者的培养上清液可促进成纤维细胞增殖，而HC的培养上清液则不促进成纤维细胞增殖。结论：SSc患者PBMC中CD161+Vδ1+γδT细胞比例较小且细胞功能改变在IP的发病机制中发挥作用。这些发现表明，CD161+Vδ1+γδ T 细胞可能通过产生 IFN-γ 在 SSc 患者 IP 的发病机制中发挥调节作用。
Objective.Interstitial pneumonia (IP) is a chronic progressive interstitial lung disease associated with high mortality and poor prognosis. However, the pathogenesis of IP remains to be elucidated. The aim of this study was to clarify the role of CD161+Vδ1+γδ T cells in SSc patients with IP.Methods.The proportion of CD161+Vδ1+γδ T cells in peripheral blood mononuclear cells (PBMCs) and serum sialylated carbohydrate antigen (KL-6) levels were determined. GeneChip analysis was performed with CD161−and CD161+Vδ1+γδ T cells. Cytokine and chemokine expression from CD161+Vδ1+γδ T cells was measured and used to evaluate the effect of culture supernatant on fibroblast proliferation.Results.The proportion of CD161+Vδ1+γδ T cells was significantly higher in SSc than healthy controls (HCs) and correlated negatively with serum KL-6 levels in IP-positive SSc patients. The gene and mRNA expression level of chemokine ligand 3 (CCL3) was markedly higher in CD161+Vδ1+γδ T cells than in CD161−Vδ1+γδ T cells. CD161+Vδ1+γδ T cells in IP-positive SSc patients showed higher production of CCL3 and lower production of IFN-γ than in HCs. Culture supernatant derived from IP-negative and IP-positive SSc patients promoted fibroblast proliferation, whereas that from HCs did not.Conclusion.The small proportion and the altered cell functions of CD161+Vδ1+γδ T cells among PBMCs in SSc patients play a role in the pathogenesis of IP. These findings suggest that CD161+Vδ1+γδ T cells may play a regulatory role in the pathogenesis of IP in SSc patients via IFN-γ production.