AIM2 deficiency in B cells ameliorates systemic lupus erythematosus by regulating Blimp-1-Bcl-6 axis-mediated B-cell differentiation  

作　　者：Ming Yang Di Long Longyuan Hu Zhidan Zhao Qianwen Li Yunkai Guo Zhenghao He Ming Zhao Liwei Lu Fen Li Hai Long Haijing Wu Qianjin Lu 

机构地区：[1]Department of Dermatology,Second Xiangya Hospital,Central South University,Hunan Key Laboratory of Medical Epigenomics,Changsha,Hunan,China [2]Department of Otolaryngology Head and Neck Surgery,Second Xiangya Hospital,Central South University,Changsha,China [3]Department of Pathology and Shenzhen Institute of Research and Innovation,The University of Hong Kong,Pok Fu Lam,Hong Kong [4]Department of Rheumatology and Immunology,Second Xiangya Hospital,Central South University,Changsha,China [5]Institute of Dermatology,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,China

出　　处：《Signal Transduction and Targeted Therapy》2021年第10期3085-3095,共11页信号转导与靶向治疗（英文）

基　　金：supported by the National Natural Science Foundation of China(Nos.81972943,81830097);Hunan Talent Young Investigator(No.2019RS2012);Hunan Outstanding Young Investigator(No.2O2OJJ2O55)CAMS Innovation Fund for Medical Sciences(CIFMS)(2019-I2M-5-033);Chongqing International Institute for Immunology(2020YJC10).

摘　　要：Absent in melanoma 2(AIM2)has been reported to be a component of inflammasomes in innate immune cells.Surprisingly,AIM2 is expressed by B cells,and higher AIM2 expression is observed in the B cells from lupus patients.To date,the inflammasome-indepe ndent functi on of AIM2 in B cells remai ns un clear.Here,we report in creased expressi on of AIM2 in human tonsil memory and germinal center(GC)B cells and in memory B cells and plasma cells from the circulation and skin lesions of lupus patients.Conditional knockout of AIM2 in B cells reduces the CD19^(+)B-cell frequency in lymph nodes and spleens,and dampens KLH-induced lgG1-antibody production.In a pristane-induced mouse model of lupus,AIM2 deficiency in B cells attenuates lupus symptoms and reduces the frequency of GC B cells,T follicular helper(Tfh)cells,plasmablast cells,and plasma cells.Furthermore,the loss of AIM2 in human B cells leads to the increased expression of Blimp-1 and reduces the expression of Bcl-6.However,the silendng of Blimp-1 and Bcl-6 has no significant effect on AIM2 expression,indicating that AIM2 might be the upstream regulator for Blimp-1 and Bcl-6.In addition,IL-10 is found to upregulate AIM2 expression via DNA demethylation.Together,our findings reveal that AIM2 is highly expressed in the B cells of lupus patients and promotes B-cell differentiation by modulating the Bcl-6-Blimp-1 axis,providing a novel target for SLE treatment.

关 键 词：LUPUS SPLEEN AIM2 

分 类 号：R593.241[医药卫生—内科学]