Leptin levels are increased in patients with systemic lupus erythematosus (SLE) but little is known on how this correlates with several disease characteristics including the frequency of regulatory T cells (Tregs). Here we compared serum leptin levels with frequency of circulating Tregs in 47 lupus patients vs. 25 healthy matched controls. Correlations with lupus disease activity were also analyzed, as well as Treg proliferation potential. It was found that leptin was remarkably increased in SLE patients as compared to controls, particularly in SLE patients with moderate and severe active SLE, and the increase correlated with disease activity. Importantly, increased leptin in lupus patients inversely correlated with the frequency of Tregs but not in controls, and leptin neutralization resulted in the expansion of Tregs ex vivo. Thus, hyperleptinemia in lupus patients correlates directly with disease activity and inversely with Treg frequency. The finding that leptin inhibition expands Tregs in SLE suggests possible inhibition of this molecule for an enhanced Treg function in the disease.
Background Inflammatory bowel diseases (IBD) is a chronic intestinal disease characterized by persistent intestinal inflammation and mucosal damage. Mesenchymal stem cells (MSCs) transplantation is a promising therapy in IBD and other autoimmune diseases. Recent studies indicated that exosomes are the main therapeutic vectors of MSCs in treatment of IBD, but the therapeutic mechanism of exosomes derived from MSCs (MSCs-EXO) remains to be explored. The aims of our research is to explore whether MSCs-EXO have a protective effect on the intestinal barrier. Methods The serum-free cell culture supernatant of Human umbilical cord MSCs (hUC-MSCs) cultured for 48 hours was collected to extract exosomes. Two separate mouse models of IBD induced by dextran sulfate sodium (DSS) and 2,4,6-trinitrobenzenesulfonic acid (TNBS) were administered MSCs-EXO intraperitoneally. The effects of MSCs-EXO on intestinal inflammation, colon barrier function and proportion of T cells were investigated. Results Intraperitoneal injection of MSCs-EXO significantly ameliorated colitis, especially reduced disease activity index and mortality, and inhibited inflammatory cells infiltration. The protective effect of MSCs-EXO on intestinal barrier was demonstrated by reducing the loss of goblet cells and the intestinal mucosa permeability, improving the destruction of tight junctions (TJs) structures and microvilli, and increasing the expression of TJs proteins ZO-1, Claudin-1, and Occludin. MSCs-EXO administration downregulated the level of proinflammatory cytokines, including CXCL14, IL-1β, IL-11, and IL-12 and upregulated the anti-inflammatory cytokine IL-4 and TGF-β in colon tissue. MSCs-EXO also modulated the response of Th2 cells and Th17 cells in mesenteric lymph nodes (MLN). Conclusion Our findings suggested that MSCs-EXO promoted mucosal barrier repair and maintained intestinal immune homeostasis in murine colitis model.
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