Curcumin chitosan microspheres regulate Th17/Treg balance via IGF2BP1- mediated m6A modification of LRP5 in ulcerative colitis

Abstract

Objective(s): Ulcerative colitis (UC) is a commonly recurrent inflammatory bowel disease. T helper 17 (Th17)/regulatory T (Treg) cell balance plays an essential role in UC progression. However, it is unknown whether curcumin chitosan microspheres (CCM) regulate the Th17/Treg cell balance.Materials and Methods: The UC mouse model was established by administering 3% dextran sodium sulfate and treated with CCM. The influence of CCM on the Th17/Treg balance was detected using flow cytometry. Cell experiments were conducted to investigate the role and mechanism of IGF2BP1 in Th17/Treg balance.Results: We revealed that CCM demonstrated a significant therapeutic effect on UC. CCM obviously decreased the Th17 cell percentage but boosted the Treg cell percentage in UC mice. CCM remarkably increased the mRNA expression of Foxp3 but suppressed RORγt and interleukin-10 mRNA expression. PCR array of RNA modification-related genes revealed that the m6A binding protein IGF2BP1 was a key molecule in CCM regulation of Th17/Treg balance. IGF2BP1 overexpression dramatically repressed the CCM-induced balance of Th17/Treg cell differentiation. Mechanically, IGF2BP1 targeted LRP5 and regulated LRP5 through m6A modification. Furthermore, the silencing of LRP5 canceled the suppressive effect of IGF2BP1 on Th17/Treg cell percentage.Conclusion: CCM modulated the Th17/Treg balance through IGF2BP1-mediated m6A modification, thereby alleviating UC, and providing new ideas for the treatment of UC.

Keywords

• inflammatory bowel disease
• medicine
• n6-methyladenosine- modification
• th17 cell
• treg cell