AIM associated with the IgM pentamer: attackers on stand-by at aircraft carrier  

作　　者：Toru Miyazaki Tomoko Yamazaki Ryoichi Sugisawa M Eric Gershwin Satoko Arai 

机构地区：[1]Laboratory of Molecular Biomedicine for Pathogenesis,Center for Disease Biology and Integrative Medicine,Faculty of Medicine,The University of Tokyo,Tokyo 113-0033,Japan [2]CREST,Japan Agency for Medical Research and Development,Tokyo 113-0033,Japan [3]Max Planck-The University of Tokyo Center for Integrative Inflammology,Tokyo 113-0033,Japan [4]Division of Rheumatology Allergy and Clinical Immunology,The University of California School of Medicine,Davis,CA 95616,USA

出　　处：《Cellular & Molecular Immunology》2018年第6期563-574,共12页中国免疫学杂志（英文版）

基　　金：This work was supported by AMED-CREST,Japan Agency for Medical Research Development(to TM),a MEXT Grant-in-Aid for Scientific Research(S)Grant number 16H06389(to TM)and(B)Grant number 16H05313(to SA).

摘　　要：Circulating immunoglobulin M(IgM)exists in a pentameric form,possessing a polyreactive nature that responds not only to foreign antigens but also to autoantigens;thus,it is involved in both beneficial and detrimental immune responses,including protection from infection and the progression of autoimmunity.On the other hand,IgM also behaves as a carrier of the apoptosis inhibitor of macrophage(AIM)protein,storing a large amount of the inactivated form of AIM in the blood through this association.Under different disease conditions,AIM can dissociate from IgM locally or systemically to exert its function,inducing the removal of various biological debris such as excess fat,bacteria,cancer cells or dead cell debris.Most typically,upon induction of acute kidney injury(AKI),IgM-free AIM is filtered by the glomerulus in the kidney,which stimulates the clearance of intraluminal dead cells debris at the obstructed proximal tubules,thereby facilitating the repair of kidney injury.Interestingly,cats exhibit a deficiency in AIM release from IgM,which may increase their susceptibility to renal failure.Conversely,association with AIM inhibits IgM binding to the Fcα/μreceptor on follicular dendritic cells at the splenic germinal center,thereby protecting the IgM immune complex from Fcα/μreceptor-mediated internalization,which supports IgM-dependent antigen presentation to B cells and stimulates high-affinity IgG antibody production.The regulation of AIM–IgM binding,resulting from the discovery of reciprocal actions between AIM and IgM,could lead to the development of novel therapies against different diseases.

关 键 词：apoptosis inhibitor of macrophage(AIM) immunoglobulin M(IgM) acute kidney injury(AKI) hepatocellular carcinoma(HCC) cat renal failure 

分 类 号：R69[医药卫生—泌尿科学]