Involvement of MST1/mTORC1/STAT1 Activity in the Regulation of B-cell Receptor Signalling by Chemokine Receptor 2

Overview

Journal Clin Transl Med

Publisher Wiley

Specialty General Medicine

Date 2022 Jul 25

PMID 35875970

Authors

Yingzi Zhu

Heng Gu

Lu Yang

Na Li

Qiuyue Chen

Danqing Kang

Shengyan Lin

Yukai Jing

Panpan Jiang

Qianglin Chen

Li Luo

Ju Liu

Jiang Chang

Zhenzhen Li

Yi Wang

Xin Dai

Heather Miller

Lisa S Westerberg

Chan-Sik Park

Masato Kubo

Quan Gong

Lingli Dong

Chaohong Liu

Affiliations

Soon will be listed here.

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.

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