IRGM/Irgm1的生物学功能研究进展

Research advances in the biological function of IRGM/Irgm1

免疫相关鸟苷三磷酸酶M蛋白(immune-related guanosine triphosphatase M protein,IRGM/Irgm1)是免疫相关GTPases(immunity related GTPases,IRGs)家族的一员。IRGs是参与机体早期免疫应答的一类蛋白,不同物种的IRGs蛋白,其家族成员也大不相同。人类体内仅进化出两个IRG基因,一个功能性的IRGM和一个不参与免疫的IRGC。然而,在小鼠体内,IRGs是一个干扰素诱导的GTPase大家族,其Irgm1(LRG-47)功能也较为广泛,主要包括广谱的抗感染与宿主防御、细胞自噬以及在部分炎性疾病中的促炎作用。大量研究发现人类IRGM蛋白与小鼠的Irgm1发挥着相似但不完全相同的生物学功能。人类IRGM基因在自噬靶向消灭结核分枝杆菌中起着重要作用,并且IRGM与克罗恩病(Crohn's disease,CD)的发病风险密切相关,现就人类IRGM/Irgm1的功能及其作用机制进行综述。

Immune-related guanosine triphosphatase M protein(IRGM/Irgm1)is a member of the immunity related GTPases(IRGs)family.IRGs are a type of proteins involved in the body's early immune response.The family members of IRGs proteins in different species are also quite different.Only two IRG genes have evolved in humans:functional IRGM and another IRGC not involved in immunity.However,in mice,the immunity-related IRGs belong to the large family of GTPase induced by interferon.The function of Irgm1(LRG-47)is more extensive in mice,mainly including broad spectrum anti-infection and host defense,cell autophagy and pro-inflammatory effect in some inflammatory diseases.A large number of studies have found that human IRGM protein and mouse Irgm1 exert similar but not identical biological functions.Human IRGM gene plays an important role in the autophagy-targeted destruction of Mycobacterium tuberculosis,and IRGM was strongly associated with the onset risk of Crohn's disease.This paper will review the functions and working mechanisms of Irgm1 in human.