Open AccessInvolvement of MST1/mTORC1/STAT1 activity in the regulation of B‐cell receptor signalling by chemokine receptor 2
Author(s) -
Zhu Yingzi,
Gu Heng,
Yang Lu,
Li Na,
Chen Qiuyue,
Kang Danqing,
Lin Shengyan,
Jing Yukai,
Jiang Panpan,
Chen Qianglin,
Luo Li,
Liu Ju,
Chang Jiang,
Li Zhenzhen,
Wang Yi,
Dai Xin,
Miller Heather,
Westerberg Lisa S.,
Park ChanSik,
Kubo Masato,
Gong Quan,
Dong Lingli,
Liu Chaohong
Publication year - 2022
Publication title -
clinical and translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
H-Index - 1
ISSN - 2001-1326
DOI - 10.1002/ctm2.887
Subject(s) - ccr2 , downregulation and upregulation , breakpoint cluster region , b cell receptor , mtorc1 , microbiology and biotechnology , chemokine receptor , immune system , biology , cancer research , b cell , pi3k/akt/mtor pathway , receptor , chemokine , signal transduction , chemistry , immunology , antibody , biochemistry , gene
Abstract Background CCR2 is involved in maintaining immune homeostasis and regulating immune function. This study aims to elucidate the mechanism by which CCR2 regulates B‐cell signalling. Methods In Ccr2 ‐knockout mice, the development and differentiation of B cells, BCR proximal signals, actin movement and B‐cell immune response were determined. Besides, the level of CCR2 in PBMC of SLE patients was analysed by bioinformatics. Results CCR2 deficiency reduces the proportion and number of follicular B cells, upregulates BCR proximal signalling and enhances the oxidative phosphorylation of B cells. Meanwhile, increased actin filaments aggregation and its associated early‐activation events of B cells are also induced by CCR2 deficiency. The MST1/mTORC1/STAT1 axis in B cells is responsible for the regulation of actin remodelling, metabolic activities and transcriptional signalling, specific MST1, mTORC1 or STAT1 inhibitor can rescue the upregulated BCR signalling. Glomerular IgG deposition is obvious in CCR2‐deficient mice, accompanied by increased anti‐dsDNA IgG level. Additionally, the CCR2 expression in peripheral B cells of SLE patients is decreased than that of healthy controls. Conclusions CCR2 can utilise MST1/mTORC1/STAT1 axis to regulate BCR signalling. The interaction between CCR2 and BCR may contribute to exploring the mechanism of autoimmune diseases.