To explore the impact of immune cells and intercellular interactions on the progression of diabetic kidney disease(DKD)in mice,this study employed CellChat software for the analysis of single-cell RNA-sequencing(scRNA-Seq)data.The investigation un-veiled,MIF signaling,one of three prominent signaling(CCL,MIF,and CXCL)between renal immune cells,witnessed a significant decline in the early DKD kidney,characterized by diminished expression of Mif and its receptor genes Cd44,Cxcr4,and Cxcr2.Addi-tionally,F13a1+macrophages ceased to be responsive to MIF signaling.In the early DKD kidney,F13a1+ macrophages were immune cells with the most pronounced differences in both interaction numbers and strength.Moreover,alterations of ligands in F13a1+macro-phages in DKD kidneys resulted in the disappearance of ANGPTL,IL2,and IL16 signaling,and the emergence of KIT and PROS sig-naling.Notably,it was observed that F13a1+macrophages reduced the expression of the transcription factor Etv1(ETS variant tran-scription factor 1),which is pivotal in regulating activity of immune cells.Gene set enrichment analysis(GSEA)of differentially ex-pressed genes(DEGs)revealed chemokine-mediated signaling pathways,immune response,and myeloid leukocyte mediated immunity were down-regulated.Meanwhile,the activation of immune response,phagocytosis,engulfment,and hematopoietic progenitor cell differ-entiation were up-regulated in F13a1+macrophages in early DKD kidney.Finally,validation using kidneys from mice with diet-induced diabetes demonstrated excellent reproducibility of the results,except for KIT signaling.This study reveals that in the kidneys of mice with early DKD,F13a1+macrophages change the immune related activity which partly links to reduced expression of transcription factor Etv1,and modulate immune-cell communication by modifying MIF signaling and the interactions of ligand-receptor pairs,including TSLP-(IL7R+CRLF2),IL16-CD4,ANGPTL4-SDC3/4,and PROS1-AXL,underscoring their crucial role in the initiation and progression of DKD.
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