MCP-1/CCR2 axis is involved in the regulation of γδT cells in lupus nephritis

Scand J Immunol. 2023 Oct;98(4):e13305. doi: 10.1111/sji.13305. Epub 2023 Jun 16.

Abstract

γδT cells are important innate immune cells that are involved in the occurrence and development of autoimmune diseases such as systemic lupus erythematosus (SLE). Lupus nephritis (LN) is a serious complication of SLE, characterized by the accumulation of immune cells (including γδT cells) in the target organs to participate in the disease process. Therefore, clarifying how γδT cells chemotactically migrate to target organs may be a key to developing therapeutic methods against LN. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of chemokines in LN patients and healthy controls. Real-time polymerase chain reaction (RT-PCR) and flow cytometry were used to measure the expression of chemokine receptors on the surface of γδT cells. The chemotactic migration ability of γδT cells was detected by Transwell assay. Signalling pathway activation of γδT cells was detected by Automated Capillary Electrophoresis Immunoassay and flow cytometry. The serum levels of chemokines, including monocyte chemoattractant protein-1 (MCP-1) in LN patients, were significantly increased. CCR2, the receptor of MCP-1, was also highly expressed on the surface of peripheral γδT cells in LN patients. In addition, the exogenous addition of MCP-1 can enhance chemotactic migration of γδT cells in LN patients. MCP-1 could activate STAT3 signalling in LN patients' peripheral γδT cells. γδT cells might participate in the pathogenesis of LN through MCP-1/CCR2 axis. This finding provides new opportunities for developing treatment methods against LN by targeting MCP-1/CCR2 axis.

Keywords: CCR2; MCP‐1; STAT3; lupus nephritis; γδ T cells.

MeSH terms

  • Chemokine CCL2
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Lupus Erythematosus, Systemic*
  • Lupus Nephritis*
  • Receptors, CCR2
  • Signal Transduction

Substances

  • Chemokine CCL2
  • CCR2 protein, human
  • Receptors, CCR2