Decreased TAX1BP1 participates in systemic lupus erythematosus by regulating monocyte/macrophage function

作者全名："Qian, Tian; Huo, Bengang; Deng, Xiaorong; Song, Xiaoli; Jiang, Yiwei; Yang, Jurong; Hao, Fei"

作者地址："[Qian, Tian; Deng, Xiaorong; Jiang, Yiwei; Hao, Fei] Chongqing Med Univ, Dermatol & Plast Surg Ctr, Affiliated Hosp 3, Chongqing 401120, Peoples R China; [Huo, Bengang; Yang, Jurong] Chongqing Med Univ, Dept Nephrol, Affiliated Hosp 3, Chongqing 401120, Peoples R China; [Song, Xiaoli] Chongqing Med Univ, Dept Rheumatol, Affiliated Hosp 3, Chongqing 401120, Peoples R China"

通信作者："Hao, F (通讯作者)，Chongqing Med Univ, Dermatol & Plast Surg Ctr, Affiliated Hosp 3, Chongqing 401120, Peoples R China.; Yang, JR (通讯作者)，Chongqing Med Univ, Dept Nephrol, Affiliated Hosp 3, Chongqing 401120, Peoples R China."

来源：INTERNATIONAL IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001101993000003

JCR分区：Q2

影响因子：4.8

年份：2023

卷号：35

期号：10

开始页：483

结束页：495

文献类型：Article

关键词：phosphoproteomic; SLE; transcriptomic

摘要："Systemic lupus erythematosus (SLE) involves disorders of innate and adaptive immune pathways. Tax1-binding protein 1 (TAX1BP1) modulates the production of antibodies in B cells and the T-cell cycle by regulating the NF-kappa B signaling pathway. However, the potential association of TAX1BP1 with SLE and its role in monocytes/macrophages have not been fully elucidated. In this study, we utilized whole-exome sequencing (WES) in combination with Sanger sequencing and identified 16 gene mutations, including in TAX1BP1, in an SLE family. TAX1BP1 protein expression with western blotting detection was reduced in SLE patients and correlated with disease activity negatively. Furthermore, RNA sequencing and 4D Label-Free Phosphoproteomic analysis were employed to characterize the transcriptome and phosphoproteome profiles in THP-1 and THP-1-differentiated M1 macrophages with TAX1BP1 knockdown. Silencing of TAX1BP1 in THP-1 and THP-1-differentiated M1 macrophages led to an increase in cluster of differentiation 80 (CD80) expression and differential changes in CD14 and CD16 expression, as assessed by flow cytometry. Additionally, western blot analysis showed that knockdown of TAX1BP1 led to a reduction in TRAF6 and p-p65 in THP-1-differentiated macrophages, with or without lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-alpha stimulation. Taken together, our findings suggest that TAX1BP1 participates in SLE activity by regulating antigen presentation in monocytes and inflammatory responses in M1 macrophages. The role of TAX1BP1 in SLE Graphical Abstract"

基金机构："The authors are grateful to the patients and the healthy-control volunteers for their participation in the study. We thank Prof. Bing Ni, Dr Mengjie Zhang, Dr Wenying Liu and Dr Shifei Li for technical assistance. We would especially like to thank Prof. Ba"

基金资助正文："The authors are grateful to the patients and the healthy-control volunteers for their participation in the study. We thank Prof. Bing Ni, Dr Mengjie Zhang, Dr Wenying Liu and Dr Shifei Li for technical assistance. We would especially like to thank Prof. Bangtao Chen for his instructive suggestions on the work."