Conjunctiva Resident γδ T Cells Expressed High Level of IL-17A and Promoted the Severity of Dry Eye.
Conjunctiva Resident γδ T Cells Expressed High Level of IL-17A and Promoted the Severity of Dry Eye.
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结膜驻留γδ T细胞高表达IL-17 A并促进干眼症的严重程度。
DOI：
10.1167/iovs.63.12.13
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发表时间：
2022-11-01
影响因子：
4.4
通讯作者：
中科院分区：
文献类型：
--
作者：
结膜炎症促进干眼病（DED）的眼表疾病。在这里，我们确定了γδ T细胞是小鼠结膜中IL-17A的主要来源，并评估了它们在DED发病机制中的作用。我们招募了22例DED患者，用流式细胞术分析了结膜上皮样品中γδ T细胞的比例。采用成年C57Bl/6野生型和TCRδ−/−小鼠诱导DED模型，研究γδ T细胞的作用。采用流式细胞术、Western blot和定量聚合酶链反应分析小鼠结膜免疫细胞浸润特征及免疫相关细胞因子或标志物的表达。在人DED结膜中，严重角膜上皮缺损患者的γδ T细胞比例明显高于轻度角膜上皮缺损患者，这在小鼠DED模型中也得到了一致的观察结果。此外，在小鼠结膜中检测到高水平的IL-17A，而不是IFN-γ。结膜上产生il - 17a增加的细胞主要为γδ T细胞，Th17细胞较少。在小鼠DED模型中，通过抗体缺失或TCRδ基因缺失来消融γδ T细胞可减轻眼表损伤。我们的研究评估了人类和实验小鼠DED，以寻找γδ T细胞介导炎症的证据，并强调了IL-17和γδ T细胞在DED治疗中的潜在治疗协同作用。
Conjunctival inflammation promotes ocular surface disorders in dry eye disease (DED). Here we identified γδ T cells as the predominant source of IL-17A in the murine conjunctiva and assessed their contribution to the pathogenesis of DED. We enrolled 22 patients with DED, and analyzed the proportion of γδ T cells in the conjunctival epithelial samples by flow cytometry. Adult C57Bl/6 wild-type and TCRδ−/− mice were used to induce DED models to investigate the role of γδ T cells. The characteristics of immune cell infiltration and the expression of immune-related cytokines or markers in mouse conjunctiva were analyzed by flow cytometry, Western blot, and quantitative polymerase chain reaction. The proportion of γδ T cells in the human DED conjunctiva is significantly higher in patients with severe corneal epithelial defects than in mild ones, which is consistently observed in the murine DED model. Further, a high level of IL-17A but not IFN-γ is detected in the conjunctiva of mice. The increased murine IL-17A–producing cells on the conjunctiva are identified as γδ T cells predominantly and Th17 cells to a lesser extent. Ablation of γδ T cells by antibody depletion or genetic deletion of TCRδ alleviates ocular surface damage in the murine DED model. Our studies evaluate human and experimental murine DED for evidence of γδ T-cell–mediated inflammation and highlight a potential therapeutic synergy by targeting IL-17 and γδ T cells in DED treatment.
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DOI：
10.1016/j.jaci.2018.03.007
发表时间：
2019-01
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Cai T;Qiu J;Ji Y;Li W;Ding Z;Suo C;Chang J;Wang J;He R;Qian Y;Guo X;Zhou L;Sheng H;Shen L;Qiu J
通讯作者：
Qiu J
影响因子：
1.2
作者：
Bose, Tanima;Hou, Aihua;Chandy, K. George
通讯作者：
Chandy, K. George
影响因子：
4.4
作者：
Inagaki-Ohara, K;Chinen, T;Yoshimura, A
通讯作者：
Yoshimura, A
影响因子：
16.6
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Akitsu A;Ishigame H;Kakuta S;Chung SH;Ikeda S;Shimizu K;Kubo S;Liu Y;Umemura M;Matsuzaki G;Yoshikai Y;Saijo S;Iwakura Y
通讯作者：
Iwakura Y
影响因子：
20.3
作者：
Chauhan, Sunil K.;Jin, Yiping;Dana, Reza
通讯作者：
Dana, Reza