Immunomodulatory effect of CD71+ erythroid cells in patients with kidney failure

Abstract

Background Immune abnormalities play a critical role in the pathogenesis of kidney failure. CD71(+) erythroid cells are known to modulate immune responses. However, their immunomodulatory effects in kidney failure patients remain unclear. Therefore, we investigated the frequencies of CD71 + erythroid cells, Th1, Th2, Th17 cells, and regulatory T cells (Tregs), as well as the impact of CD71 + erythroid cells on the proliferation of peripheral blood mononuclear cells (PBMCs) of kidney failure patients. Methods PBMCs were isolated from 49 kidney failure patients and 20 healthy subjects. The frequencies of T cell subsets and CD71 + erythroid cells were determined by flow cytometry. The numbers of reticulocytes and RBCs were also measured. Panel-reactive antibodies screening was used to assess antibodies against human leukocyte antigens (HLAs) in the patients. The effect of CD71 + erythroid cells on PBMC proliferation in kidney failure patients was investigated using a CFSE labeling assay. Erythropoietin level was measured by ELISA. Results Kidney failure patients showed a significant increase in CD71 + erythroid cells (P < 0.01). In contrast, the frequencies of Th1, Th2, and Th17 cells were significantly reduced in these patients (P < 0.01-0.05). Among CD4 + T subsets, Th1 cell frequency was inversely correlated with the number of CD71 + erythroid cells (P < 0.05). In vitro, CD71 + erythroid cells inhibited the proliferation of PMBCs in kidney failure patients (P < 0.0001-0.05). No significant difference was observed in Treg frequencies between patients and controls. The frequency of CD71 + erythroid cells was significantly decreased in kidney failure patients with anti-HLA antibodies, unlike patients without anti-HLA antibodies (P < 0.001). The patients had an increased number of reticulocytes, unlike RBC, in peripheral blood compared with healthy subjects (P < 0.01-0.05). The patients exhibited a reduction in erythropoietin level compared with the control group (P < 0.0001). Conclusion These findings suggest CD71 + erythroid cells may contribute to immune dysregulation in kidney failure patients, potentially playing a role in disease progression and its immunopathology.