类风湿关节炎是慢性全身性自身免疫疾病,由于免疫系统异常活化引发的炎症反应会导致关节滑膜的血管翳形成,并逐渐出现骨及软骨破坏,临床表现为患者的多关节疼痛、肿胀、甚至畸形,影响患者生活质量,最终可致关节功能丧失。其起病和复发的主要原因是免疫系统产生针对自身抗原的免疫细胞、细胞因子以及抗体等,其中NLRP3炎症小体在炎症反应中扮演着关键角色。NEK7激酶作为NLRP3的结合蛋白,作用于K+外流的下游,调节NLRP3的寡聚和激活,是NLRP3炎性小体激活必不可少的激酶,但关于NEK7通过激活NLRP3炎症小体进而参与类风湿关节炎炎症活动的相关研究目前尚无报道。本文就NLRP3炎症小体激活、NEK7激酶调节NLRP3炎症小体激活过程的研究进展进行综述,以期为NEK7激活NLRP3炎症小体对类风湿关节炎炎症活动的认识以及今后的靶点治疗相关研究提供新的思路。
Rheumatoid arthritis is a chronic systemic autoimmune disease. The inflammatory response caused by the abnormal activation of the immune system will lead to the formation of pannus in the synovium of the joints, and the gradual destruction of bone and cartilage. The clinical manifestations are pain and swelling of multiple joints, or even deformity, affect the quality of life of patients, and eventually lead to loss of joint function. The main reason for its onset and recurrence is that the immune system produces immune cells, cytokines and antibodies against self-antigens, among which the NLRP3 inflammasome plays a key role in the inflammatory response. As a binding protein of NLRP3, NEK7 kinase acts downstream of K+ efflux and regulates the oligomerization and activation of NLRP3 inflammasomes. However, there have been no report on the involvement of NEK7 in the inflammatory activities of rheumatoid arthritis through the activation of NLRP3 inflammasomes. This article reviews the research progress of NLRP3 inflammasome activation and NEK7 kinase regulating the process of NLRP3 inflammasome activation, in order to provide new insights for the understanding of NLRP3 inflammasome activation by NEK7 on inflammatory activity in rheumatoid arthritis and future research related to targeted therapy.
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