Immunological function of familial Mediterranean fever disease protein Pyrin  

作　　者：YANG Jie Ling XU Hao SHAO Feng 

机构地区：[1]National Institute of Biological Sciences [2]National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences

出　　处：《Science China(Life Sciences)》2014年第12期1156-1161,共6页中国科学（生命科学英文版）

基　　金：supported in part by an International Early Career Scientist grant from the Howard Hughes Medical Institute;the Beijing Scholar Program to Shao Feng;Other financial supports include the National Basic Research Program of China(2012CB518700),;the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB08020202);National Science Fund for Distinguished Young Scholars(31225002)to Shao Feng

摘　　要：Pyrin,encoded by MEFV gene,is conserved in humans and mice.Mutations in the MEFV gene are associated with the human autoinflammatory disease familial Mediterranean fever(FMF).Pyrin can interact with the inflammasome adaptor ASC and induce inflammatory caspase-1 activation in monocytic cells,but the physiological function of Pyrin has been unknown for many years.Here we summarize previous studies of Pyrin function under the context of FMF and immunity,and discuss a recent study demonstrating that Pyrin forms an inflammasome complex for caspase-1 activation in innate immunity.Pyrin inflammasome detects inactivating modifications of host Rho GTPases by diverse bacterial toxins and infections,including Clostridium difficile glucosylating cytotoxin Tcd B,FIC-domain adenylyltransferase effectors from Vibrio parahaemolyticus and Histophilus somni,ADP-ribosylating Clostridium botulinum C3 toxin as well as Burkholderia cenocepacia infection.The mode of Pyrin action,i.e.,sensing pathogen virulence activity rather than directly recognizing a microbial molecule,represents a new paradigm in innate immunity.Pyrin,encoded by MEFV gene,is conserved in humans and mice.Mutations in the MEFV gene are associated with the human autoinflammatory disease familial Mediterranean fever（FMF）.Pyrin can interact with the inflammasome adaptor ASC and induce inflammatory caspase-1 activation in monocytic cells,but the physiological function of Pyrin has been unknown for many years.Here we summarize previous studies of Pyrin function under the context of FMF and immunity,and discuss a recent study demonstrating that Pyrin forms an inflammasome complex for caspase-1 activation in innate immunity.Pyrin inflammasome detects inactivating modifications of host Rho GTPases by diverse bacterial toxins and infections,including Clostridium difficile glucosylating cytotoxin Tcd B,FIC-domain adenylyltransferase effectors from Vibrio parahaemolyticus and Histophilus somni,ADP-ribosylating Clostridium botulinum C3 toxin as well as Burkholderia cenocepacia infection.The mode of Pyrin action,i.e.,sensing pathogen virulence activity rather than directly recognizing a microbial molecule,represents a new paradigm in innate immunity.

关 键 词：PYRIN MEFV Rho GTPase INFLAMMASOME Guard Model 

分 类 号：R512.8[医药卫生—内科学]