Sun Tiantian, Zhang Donglei, Yang Yanhui, Zhang Xian, Lv Cuicui, Fu Rongfeng, Lv Mingen, Liu Wenjie, Chen Yunfei, Liu Wei, Huang Yueting, Xue Feng, Liu Xiaofan, Zhang Lei, Li Huiyuan, Yang Renchi
State Key Laboratory of Experimental Haematology, Institute of Haematology and Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
Br J Haematol. 2015 Apr;169(2):278-85. doi: 10.1111/bjh.13292. Epub 2015 Jan 29.
Primary immune thrombocytopenia (ITP) is an autoimmune disorder. Interleukin-35 (IL35) can suppress T cell proliferation and elicit the development of inducible regulatory T cells (Tregs). Previous studies have shown decreased plasma IL35 levels and dysfunctional T cells in patients with ITP. In this study, we determined whether decreased IL35 levels correlate with T cell dysfunction in ITP patients. Plasma IL35 levels were found to be lower in ITP patients than in healthy controls, were positively correlated with platelet levels and the percentage of peripheral circulating Tregs, and negatively correlated with the levels of T helper-1 cells in ITP patients. We also evaluated the effects of IL35 on cytokines contributing to T cell proliferation. IL35 promoted the secretion of interleukin 10 (IL10) and transforming growth factor-β1 but reduced the levels of interferon-γ and IL17A (also termed IL17). Moreover, IL35 inhibited the proliferation of CD4+ and CD8+ T cells but induced the differentiation and proliferation of Tregs in ITP. In summary, IL35 appears to contribute to the loss of immunological self-tolerance in ITP patients by modulating T cells and immunoregulatory cytokines.
原发性免疫性血小板减少症(ITP)是一种自身免疫性疾病。白细胞介素-35(IL35)可抑制T细胞增殖并诱导诱导性调节性T细胞(Tregs)的发育。先前的研究表明,ITP患者血浆IL35水平降低且T细胞功能异常。在本研究中,我们确定了IL35水平降低是否与ITP患者的T细胞功能障碍相关。结果发现,ITP患者的血浆IL35水平低于健康对照,与血小板水平和外周循环Tregs百分比呈正相关,与ITP患者辅助性T1细胞水平呈负相关。我们还评估了IL35对促成T细胞增殖的细胞因子的影响。IL35促进白细胞介素10(IL10)和转化生长因子-β1的分泌,但降低干扰素-γ和IL17A(也称为IL17)的水平。此外,IL35抑制ITP中CD4 +和CD8 + T细胞的增殖,但诱导Tregs的分化和增殖。总之,IL35似乎通过调节T细胞和免疫调节细胞因子导致ITP患者免疫自我耐受的丧失。