IL-7 Promotes the Expansion of Circulating CD28- Cytotoxic T Lymphocytes in Patients With IgG4-Related Disease via the JAK Signaling.
IL-7 Promotes the Expansion of Circulating CD28- Cytotoxic T Lymphocytes in Patients With IgG4-Related Disease via the JAK Signaling.
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IL-7 通过 JAK 信号传导促进 IgG4 相关疾病患者循环 CD28 细胞毒性 T 淋巴细胞的扩增
DOI：
10.3389/fimmu.2022.922307
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
本研究旨在阐明IgG4相关性疾病（IgG4 - RD）患者循环中CD28⁻细胞毒性T淋巴细胞（CTLs）的变化及相关机制。
研究招募了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），采用流式细胞术检测循环中CD28⁻ CTLs的水平，同时分析CD127低表达或GZMB⁺CD28⁻ CTL亚群的比例。在机制研究方面，从IgG4 - RD患者中分离出的PBMCs在有或无JAK抑制剂托法替布的情况下，用白细胞介素 - 7（IL - 7）进行刺激。运用流式细胞术分析CD28⁻ CTLs的增殖情况以及相关亚群的变化。
与健康对照者相比，IgG4 - RD患者循环中的CD4⁺CD28⁻ CTLs和CD8⁺CD28⁻ CTLs显著增多，同时CD127低表达或GZMB⁺ CTL亚群也有所升高。PBMCs的体外培养显示，IL - 7可诱导IgG4 - RD患者体内CD4⁺CD28⁻ CTLs和CD8⁺CD28⁻ CTLs扩增。此外，IL - 7可促进该疾病中这些CD28⁻ CTLs的增殖和功能亚群变化。选择性JAK抑制剂托法替布可显著抑制IL - 7对CD4⁺CD28⁻ CTLs和CD8⁺CD28⁻ CTLs的作用。
IL - 7可通过JAK通路促进IgG4 - RD患者体内CD4⁺CD28⁻和CD8⁺CD28⁻ CTLs的扩增及功能，进而影响IgG4 - RD患者的免疫平衡。阻断IL - 7信号通路可能是IgG4 - RD的一种新治疗策略。
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 ex vivo 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.
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影响因子：
7.7
作者：
Serroukh Y;Gu-Trantien C;Hooshiar Kashani B;Defrance M;Vu Manh TP;Azouz A;Detavernier A;Hoyois A;Das J;Bizet M;Pollet E;Tabbuso T;Calonne E;van Gisbergen K;Dalod M;Fuks F;Goriely S;Marchant A
通讯作者：
Marchant A
影响因子：
5.1
作者：
Kamekura R;Takahashi H;Ichimiya S
通讯作者：
Ichimiya S
DOI：
10.1002/art.40469
发表时间：
2018-07
期刊：
Arthritis & rheumatology (Hoboken, N.J.)
影响因子：
--
作者：
Della-Torre E;Bozzalla-Cassione E;Sciorati C;Ruggiero E;Lanzillotta M;Bonfiglio S;Mattoo H;Perugino CA;Bozzolo E;Rovati L;Arcidiacono PG;Balzano G;Lazarevic D;Bonini C;Falconi M;Stone JH;Dagna L;Pillai S;Manfredi AA
通讯作者：
Manfredi AA
DOI：
10.1073/pnas.1222303110
发表时间：
2013-05-07
影响因子：
11.1
作者：
Lundstrom, Wangko;Highfill, Steven;Mackall, Crystal L.
通讯作者：
Mackall, Crystal L.
影响因子：
5.5
作者：
Maritati, Federica;Peyronel, Francesco;Vaglio, Augusto
通讯作者：
Vaglio, Augusto