IL-6/IL-6R信号通路在移植排斥反应中作用研究进展

Research progress on the role of IL-6/IL-6R signaling pathway in transplant rejection

细胞因子在免疫系统中起重要作用。IL-6及其受体(IL-6/IL-6R)信号通路可以促进初始CD4+T淋巴细胞分化为Th17细胞和抑制其分化为调节性T淋巴细胞,且在B淋巴细胞分化为浆细胞产生抗体的过程中起关键作用。Th17细胞以及浆细胞产生的抗体可引起移植排斥反应,包括细胞介导的排斥反应和抗体介导的排斥反应。大量基础和临床研究证实通过阻断IL-6/IL-6R信号通路可以减轻排斥反应,特别是慢性抗体介导的排斥。因为慢性抗体介导的排斥是目前导致移植物失功的重要因素且无其他有效治疗方法,所以通过阻断IL-6/IL-6R信号通路减轻慢性抗体介导的排斥方案有望在临床进行进一步验证和推广,改善移植物预后。

Cytokines play a critical role in the immune system.IL-6/IL-6R signaling pathway can promote the differentiation of naive CD4+T cells into T-helper 17 cells(Th17),whereas inhibit the differentiation of these cells into regulatory T cells.Moreover,IL-6/IL-6R signaling pathway plays a pivotal role in the process of B cell differentiation into plasma cells,which produced antibodies.Th17 cells and antibodies produced by plasma cells can induce transplant rejection,including cell-mediated rejection and antibodymediated rejection.Substantial basic and clinical studies have demonstrated the therapeutic effect of blockade of IL-6/IL-6R signaling pathway on mitigating rejection,especially the chronic antibody-mediated rejection.Chronic antibody-mediated rejection is recognized as an important factor of graft dysfunction and lacks of effective treatment method currently.Therefore,it is expected to further verify and promote the protocol to alleviate chronic antibody-mediated rejection by blocking the IL-6/IL-6R signal pathway,and improve the prognosis of transplantation graft.