Glucose promotes Treg differentiation and suppresses intestinal inflammation

Abstract

Abstract Glucose, the most abundant monosaccharide, has been characterized as the most important source of energy in human body, which is also considered as a potential risk factor in varies of diseases. However, the roles of glucose in regulation of intestinal T cell responses and inflammation are still controversial. In this report, we investigated whether and how glucose regulates the CD4+ T cell responses in intestinal inflammation. We treated Rag−/− mice which were transferred with CBir1 CD4+ T cells, which are specific for immunodominant microbiota antigen CBir1 flagellin, with drinking water with or without 0.6% or 6% (w/v) glucose for two weeks. We found that 6%, but not 0.6%, glucose in drinking water promoted regulatory T cells (Treg), but not Th1 and Th17 cells, differentiation in the mesenteric lymph nodes (MLN). In vivo administration of glucose to WT mice at the dose of 6%, but not 0.6%, also increased Treg cells in MLN. Within in vitro assay, glucose promoted Treg differentiation in a dose-dependent manner from 4500ug/ml to 15000ug/ml, but inhibited Treg differentiation with the dose higher than 15000ug/ml. Moreover, glucose-treated T cells cultured under Treg conditions showed enhanced suppressive activity toward naïve T cell proliferation. Mechanistically, glucose upregulated the expression of EGFR, Areg and Gzmb, the genes associated with regulation of Treg suppressive function. Furthermore, glucose at the dose of 6% alleviated the colitis in RAG−/− mice induced by CBir1 T cells, and increased Treg, but not Th1 and Th17, cells in MLN. Collectively, our study indicates that glucose promotes Treg differentiation and function under certain conditions, which plays an important role in intestinal homeostasis.