Suppressor of cytokine signaling-1 mimetic peptides attenuate lymphocyte activation in the MRL/lpr mouse autoimmune model.
Suppressor of cytokine signaling-1 mimetic peptides attenuate lymphocyte activation in the MRL/lpr mouse autoimmune model.
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DOI：
10.1038/s41598-021-86017-4
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发表时间：
2021-03-18
影响因子：
4.6
通讯作者：
Larkin J 3rd
中科院分区：
文献类型：
--
作者：
Sharma J;Collins TD;Roach T;Mishra S;Lam BK;Mohamed ZS;Veal AE;Polk TB;Jones A;Cornaby C;Haider MI;Zeumer-Spataro L;Johnson HM;Morel LM;Larkin J 3rd
自身免疫性疾病主要由异常激活的淋巴细胞产生的致病性细胞因子环境驱动。许多细胞因子，包括干扰素γ（IFN-γ），利用JAK/STAT途径进行信号传播。细胞因子信号转导抑制因子-1（SOCS 1）是一种可诱导的细胞内蛋白，通过抑制JAK/STAT信号转导来调节IFN-γ信号转导。使用Fas缺陷型MRL/MpJ-Faslpr/J（MRL/lpr）小鼠，自发地发展狼疮样疾病，我们测试了SOCS 1激酶抑制区（SOCS 1-KIR）的肽模拟物将抑制淋巴细胞活化并调节狼疮相关病理的假设。与体外研究一致，SOCS 1-KIR腹膜内给药降低了外周血、脾和淋巴结内记忆性CD 8+和CD 4 + T淋巴细胞的频率、活化和细胞因子产生。此外，SOCS 1-KIR给药减少了淋巴结病、皮肤病变的严重程度、自身抗体的产生，并适度减少了肾脏病理。在细胞水平上，腹膜SOCS 1-KIR给药增强了总脾和滤泡调节性T细胞中Foxp 3的表达，降低了CD 4+和CD 8+细胞的效应记忆/幼稚T淋巴细胞比率，并降低了GL 7+生发中心富集的B细胞的频率。总之，这些数据表明SOCS 1-KIR治疗降低了自身反应性淋巴细胞效应子功能，并表明通过肽施用的SOCS 1途径的治疗靶向可能在减轻自身免疫性病理方面具有功效。
Autoimmune diseases are driven largely by a pathogenic cytokine milieu produced by aberrantly activated lymphocytes. Many cytokines, including interferon gamma (IFN-γ), utilize the JAK/STAT pathway for signal propagation. Suppressor of Cytokine Signaling-1 (SOCS1) is an inducible, intracellular protein that regulates IFN-γ signaling by dampening JAK/STAT signaling. Using Fas deficient, MRL/MpJ-Faslpr/J (MRL/lpr) mice, which develop lupus-like disease spontaneously, we tested the hypothesis that a peptide mimic of the SOCS1 kinase inhibitory region (SOCS1-KIR) would inhibit lymphocyte activation and modulate lupus-associated pathologies. Consistent with in vitro studies, SOCS1-KIR intraperitoneal administration reduced the frequency, activation, and cytokine production of memory CD8+ and CD4+ T lymphocytes within the peripheral blood, spleen, and lymph nodes. In addition, SOCS1-KIR administration reduced lymphadenopathy, severity of skin lesions, autoantibody production, and modestly reduced kidney pathology. On a cellular level, peritoneal SOCS1-KIR administration enhanced Foxp3 expression in total splenic and follicular regulatory T cells, reduced the effector memory/naïve T lymphocyte ratio for both CD4+ and CD8+ cells, and reduced the frequency of GL7+ germinal center enriched B cells. Together, these data show that SOCS1-KIR treatment reduced auto-reactive lymphocyte effector functions and suggest that therapeutic targeting of the SOCS1 pathway through peptide administration may have efficacy in mitigating autoimmune pathologies.
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影响因子：
30.5
作者：
Chang, Jae-Hoon;Xiao, Yichuan;Hu, Hongbo;Jin, Jin;Yu, Jiayi;Zhou, Xiaofei;Wu, Xuefeng;Johnson, Howard M.;Akira, Shizuo;Pasparakis, Manolis;Cheng, Xuhong;Sun, Shao-Cong
通讯作者：
Sun, Shao-Cong
DOI：
10.4049/jimmunol.1102885
发表时间：
2012-05-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Good-Jacobson KL;Song E;Anderson S;Sharpe AH;Shlomchik MJ
通讯作者：
Shlomchik MJ
影响因子：
4.8
作者：
Cornish, AL;Chong, MM;Alexander, WS
通讯作者：
Alexander, WS
影响因子：
4.4
作者：
Chodisetti, Sathi Babu;Fike, Adam J.;Rahman, Ziaur S. M.
通讯作者：
Rahman, Ziaur S. M.
影响因子：
20.3
作者：
Chong, MMW;Metcalf, D;Kay, TWH
通讯作者：
Kay, TWH