2. Academic Validation
  3. Involvement of MST1/mTORC1/STAT1 activity in the regulation of B-cell receptor signalling by chemokine receptor 2

Involvement of MST1/mTORC1/STAT1 activity in the regulation of B-cell receptor signalling by chemokine receptor 2

  • Clin Transl Med. 2022 Jul;12(7):e887. doi: 10.1002/ctm2.887.
Yingzi Zhu 1,  Heng Gu 2,  Lu Yang 2,  Na Li 3,  Qiuyue Chen 3,  Danqing Kang 2,  Shengyan Lin 1,  Yukai Jing 2,  Panpan Jiang 2,  Qianglin Chen 3,  Li Luo 2,  Ju Liu 2,  Jiang Chang 2,  Zhenzhen Li 2,  Yi Wang 2,  Xin Dai 2,  Heather Miller 4,  Lisa S Westerberg 5,  Chan-Sik Park 6,  Masato Kubo 7,  Quan Gong 3,  Lingli Dong 1,  Chaohong Liu 2
Affiliations

Affiliations

  • 1 Department of Rheumatology and Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 2 Department of Pathogen Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 3 Department of Immunology, School of Medicine, Yangtze University, Jingzhou, China.
  • 4 Department of Research and Development, BD Biosciences, San Jose, California, United States.
  • 5 Department of Microbiology Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
  • 6 Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Songpa-gu, Seoul, Korea.
  • 7 Laboratory for Cytokine Regulation, Center for Integrative Medical Science (IMS), RIKEN Yokohama Institute, Kanagawa, Japan.
PMID: 35875970 DOI: 10.1002/ctm2.887
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.

Keywords

B-cell receptor; CCR2; MST1; autoimmune diseases; mTORC1.

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