IL-7 促进 IgG4 相关疾病患者循环 CD28-细胞毒性 T 淋巴细胞的扩增：JAK 信号通路的作用。
IL-7 Promotes the Expansion of Circulating CD28- Cytotoxic T Lymphocytes in Patients With IgG4-Related Disease the JAK Signaling.
机构信息
Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China.
Department of Rheumatology and Immunology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
出版信息
Front Immunol. 2022 Jul 7;13:922307. doi: 10.3389/fimmu.2022.922307. eCollection 2022.
OBJECTIVES
This study aimed to elucidate the changes and associated mechanisms of circulating CD28- cytotoxic T lymphocytes (CTLs) in patients with IgG4-related disease (IgG4-RD).
METHODS
Fifty IgG4-RD patients and 15 healthy controls (HCs) were recruited. Peripheral blood mononuclear cells (PBMCs) were isolated, the levels of circulating CD28- CTLs were detected by flow cytometry, and the proportions of CD127lo or GZMB+CD28- CTL subsets were analyzed in the meantime. Mechanistically, PBMCs isolated from IgG4-RD patients were stimulated with IL-7 in the presence or absence of the JAK inhibitor tofacitinib. Flow cytometry was used to analyze the proliferation of CD28- CTLs and the changes in related subpopulations.
RESULTS
Circulating CD4+CD28- CTLs and CD8+CD28- CTLs were significantly increased in IgG4-RD patients compared with HCs, accompanied by an elevation of CD127lo or GZMB+ CTL subsets. The culture of PBMCs showed that IL-7 could induce the amplification of CD4+CD28- CTLs and CD8+CD28- CTLs in IgG4-RD. Furthermore, IL-7 promotes the proliferation and functional subset changes of these CD28- CTLs in this disease. The selective JAK inhibitor tofacitinib significantly inhibited the effects of IL-7 on CD4+CD28- CTLs and CD8+CD28- CTLs.
CONCLUSION
IL-7 can affect the immune balance of IgG4-RD patients by promoting the expansion and function of CD4+CD28- and CD8+CD28- CTLs in IgG4-RD through the JAK pathway. Blockade of the IL-7 signaling pathway may be a new therapeutic strategy for IgG4-RD.
目的
本研究旨在阐明 IgG4 相关疾病（IgG4-RD）患者循环 CD28-细胞毒性 T 淋巴细胞（CTLs）的变化及其相关机制。
方法
招募了 50 例 IgG4-RD 患者和 15 名健康对照者（HCs）。分离外周血单个核细胞（PBMCs），通过流式细胞术检测循环 CD28-CTLs 的水平，同时分析 CD127lo 或 GZMB+CD28-CTL 亚群的比例。从 IgG4-RD 患者中分离出的 PBMCs 在存在或不存在 JAK 抑制剂托法替尼的情况下，用 IL-7 刺激，通过流式细胞术分析 CD28-CTLs 的增殖和相关亚群的变化。
结果
与 HCs 相比，IgG4-RD 患者的循环 CD4+CD28-CTLs 和 CD8+CD28-CTLs 明显增加，同时伴有 CD127lo 或 GZMB+CTL 亚群的升高。PBMCs 的培养表明，IL-7 可以诱导 IgG4-RD 中 CD4+CD28-CTLs 和 CD8+CD28-CTLs 的扩增。此外，IL-7 促进了这些 CD28-CTLs 在该疾病中的增殖和功能亚群的变化。选择性 JAK 抑制剂托法替尼显著抑制了 IL-7 对 CD4+CD28-CTLs 和 CD8+CD28-CTLs 的作用。
结论
IL-7 通过 JAK 途径促进 IgG4-RD 中 CD4+CD28-和 CD8+CD28-CTLs 的扩增和功能，影响 IgG4-RD 患者的免疫平衡。阻断 IL-7 信号通路可能是 IgG4-RD 的一种新的治疗策略。
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