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Abstract: PO1249

CD4+ ICOS-Expressing T Cells Contribute to Peritoneal Fibrosis in Patients Receiving Peritoneal Dialysis

Session Information

Category: Dialysis

  • 703 Dialysis: Peritoneal Dialysis

Authors

  • Li, Yongjie, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
  • Song, Jun, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
  • Lin, Hongchun, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
  • Peng, Hui, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
Background

Long-term peritoneal dialysis (LPD) can affect the morphology and function of the peritoneum, which causes peritoneal fibrosis one of the major causes of peritoneal dialysis (PD) failure. Reliable treatment strategies that successfully prevent progressive peritoneal fibrosis are still lacking. We performed single-cell RNA sequencing (scRNA-seq) on PD fluid from patients at different stages.

Methods

Firstly, PD fluid from patients with short-term peritoneal dialysis (SPD) (< 6 months) and LPD (>4 years) were collected for scRNA-seq analysis, and genomic expression differences of each sample were observed and analyzed. Secondly, peritoneum of PD patients and healthy inpatients were collected, and the expression of ICOS on CD4+ T cells and ICOSL, COL1A1, COL1A2, FN, CDH, IL6 on peritoneal mesothelial cells (MSC) was detected by qPCR, ELISA, flow cytometry and immunofluorescence. Thirdly, ICOS+CD4+T cells and ICOS-CD4+ T cells in PD fluid were co-cultured with MSC cell lines, then stimulated with anti-ICOS monoclonal antibody. Lastly, we used gene pathway analysis and KEGG analysis to find out the possible mechanism pathway.

Results

A total of 13,167 T cells and 6,096 MSC from 8 PD fluid biopsies were included. Through scRNA-seq analysis, we found that under the stimulation of high glucose and other components in PD fluid, compared with SPD patients, the proportion of ICOS+CD4+ T cells within T cells and ICOSL+ MSC within MSC from LPD patients was respectively increased by multiple of 0.58 and 0.29. Furthermore, the expression of COL1A1, COL1A2, FN, IL6 also increased in PD fluid and peritoneum from LPD patients. CD4+ ICOS-expressing T cells interact with MSC by increasing the expression of profibrogenic proteins through ICOS/ICOSL pathway, then accelerate the progress of peritoneal fibrosis, anti-ICOS antibody can terminate these processes.

Conclusion

CD4+ ICOS-expressing T cells contribute to peritoneal fibrosis, the anti-ICOS antibody can alleviate peritoneal fibrogenesis by interfering with the interaction between MSC and ICOS+CD4+ T cells, providing a new therapeutic target for progressive peritoneal fibrosis.

ICOS expression in T cells from SPD and LPD patients