C5a enhances Vδ1 T cells recruitment via the CCL2-CCR2 axis in IgA nephropathy

Shuanglinzi Deng; Fangyu Zhou; Fangyuan Wang; Yuanyuan Jiang; Jiale Tang; Xinyue Hu; Liying Luo; Yanli Jin; Lingyu Huang; Danni Sun; Gong Xiao; Juntao Feng; Xiaozhao Li

doi:10.1016/j.intimp.2023.111065

C5a enhances Vδ1 T cells recruitment via the CCL2-CCR2 axis in IgA nephropathy

Int Immunopharmacol. 2023 Dec;125(Pt A):111065. doi: 10.1016/j.intimp.2023.111065. Epub 2023 Oct 18.

Authors

Affiliations

¹ Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
² Department of Nephrology, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
³ Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁴ Department of Nephrology, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.. Electronic address: lixiaozhao@csu.edu.cn.

PMID: 37862725
DOI: 10.1016/j.intimp.2023.111065

Abstract

Background: Mucosal immune-associated γδ T cells have been implicated in IgA nephropathy (IgAN). However, the involvement of Vδ1 T cells, the major γδ T cells subtype, in renal damage and the mechanism underlying their migration from peripheral blood to kidney in IgAN remain unclear.

Methods: Clinical data from IgAN patients and healthy controls (HC) were analyzed. Phenotypes and chemokine receptors of γδ T cell were compared between IgAN patients and HC. Immunohistochemistry and immunofluorescence were performed to assess the infiltration of γδ T cell subsets and the expression of chemokine in renal tissues. In vitro, C5a was used to stimulate the human glomerular mesangial cells (HMCs) and chemotaxis experiment was used to examine Vδ1 T cells migration. Correlation between Vδ1 T cells and related clinical indicators were analyzed.

Results: IgAN patients exhibited decreased Vδ1 T cell in blood but increased levels in kidneys compared to HC. Increased CCR2-expressing Vδ1 T cells and serum level of CCL2 were observed in IgAN patients. CCL2 co-localized with CCR2 in HMCs of IgAN. In vitro, C5a enhanced Vδ1 T cells recruitment by HMCs through CCL2-CCR2 axis. Importantly, circulating Vδ1 T cell levels showed a negatively correlated with both the urinary protein creatinine ratio (UACR) and 24-hour urine protein (UP). Moreover, kidney infiltration of Vδ1 cells positively correlated with UACR, UP, mesangial hyperplasia and renal tubule atrophy/interstitial fibrosis in IgAN.

Conclusions: C5a-induced production of CCL2 by HMCs facilitates Vδ1 T cells recruitment via the CCL2-CCR2 axis, contributing to renal damage in IgAN.

Keywords: C5a; CCL2; IgA nephropathy; Vδ1 T cell.

MeSH terms

Chemokine CCL2
Chemokines
Glomerulonephritis, IGA* / genetics
Humans
Kidney / metabolism
Mesangial Cells / metabolism
Receptors, CCR2
T-Lymphocyte Subsets / metabolism

Substances

CCL2 protein, human
CCR2 protein, human
Chemokine CCL2
Chemokines
Receptors, CCR2
C5AR1 protein, human