IKZF1基因与SLE发病机制相关性的研究进展

A System Review on the Association Between the Critical Role of IKZF1 and the Pathogenesis of Systemic Lupus Erythematosus

IKZF1基因编码的Ikaros锌指蛋白是淋巴细胞转录因子,有调节淋巴细胞发育、分化和血液肿瘤抑制的作用。本课题组对SLE进行的GWAS研究发现IKZF1基因遗传变异体与SLE有相关性,且有研究表明IKZF1基因的低表达可能在激活信号传导通路中起关键作用,如SLE发病中涉及的STAT4和干扰素信号传导通路。此外IKZF1基因参与多种血液学的异常改变,如红细胞数目异常、急性淋巴细胞白血病(ALL)、骨髓纤维化,这些血液异常既可能是SLE患者的临床表型,也可能是与SLE同时罹患的血液病。本文将在现有IKZF1基因研究基础上,讨论其与SLE发病机制的相关性,为开展下一步研究提供思路,也为将来研发新的SLE治疗靶点提供有益的视角。

Ikaros family zinc finger 1, encoded by IKZF1, are lymphoid transcription factors playing an essential role in lymphoid lineage development, differentiation and hematological tumor suppressor. Our genome-wide associ- ation studies in systemic lupus erythematosus （SLE） independently identified genetic variants in IKZF1 asso- ciated with SLE. And some studies found that lower expression of IKZF1 may play critical roles in activating some signal t,athways involved in SLE, such as signal transducers and activators of transcription STAT4 and interferon p,,thways. In addition,IKZF1 has been implicated in roles involved in some hematologic traits or abnormalities, such as erythrocyte measures, myelofibrosis, and acute lymphoblastic leukemia （ALL）, which may be common clinical manifestations or co-occurrence hematological diseases of patients with SLE. All these findings suggest that IKZF1 may play a critical role in the pathogenesis of SLE. In this article, we discuss the role of IKZF1 in the physiological and pathological functions associated with SLE based on the ex- isting understanding of IKZF1 ,providing new insights that may assist in the development of new therapeutic targets for patients with SLE.