Curcumin chitosan microspheres regulate Th۱۷/Treg balance via IGF۲BP۱- mediated m۶A modification of LRP۵ in ulcerative colitis

Objective(s): Ulcerative colitis (UC) is a commonly recurrent inflammatory bowel disease. T helper ۱۷ (Th۱۷)/regulatory T (Treg) cell balance plays an essential role in UC progression. However, it is unknown whether curcumin chitosan microspheres (CCM) regulate the Th۱۷/Treg cell balance.Materials and Methods: The UC mouse model was established by administering ۳% dextran sodium sulfate and treated with CCM. The influence of CCM on the Th۱۷/Treg balance was detected using flow cytometry. Cell experiments were conducted to investigate the role and mechanism of IGF۲BP۱ in Th۱۷/Treg balance.Results: We revealed that CCM demonstrated a significant therapeutic effect on UC. CCM obviously decreased the Th۱۷ cell percentage but boosted the Treg cell percentage in UC mice. CCM remarkably increased the mRNA expression of Foxp۳ but suppressed RORγt and interleukin-۱۰ mRNA expression. PCR array of RNA modification-related genes revealed that the m۶A binding protein IGF۲BP۱ was a key molecule in CCM regulation of Th۱۷/Treg balance. IGF۲BP۱ overexpression dramatically repressed the CCM-induced balance of Th۱۷/Treg cell differentiation. Mechanically, IGF۲BP۱ targeted LRP۵ and regulated LRP۵ through m۶A modification. Furthermore, the silencing of LRP۵ canceled the suppressive effect of IGF۲BP۱ on Th۱۷/Treg cell percentage.Conclusion: CCM modulated the Th۱۷/Treg balance through IGF۲BP۱-mediated m۶A modification, thereby alleviating UC, and providing new ideas for the treatment of UC.

Keywords:

Inflammatory bowel disease , medicine , N۶-methyladenosine- modification , Th۱۷ cell , Treg cell