Diabetes Regulates Nlrp3/T Cell Senescence To Promote Periapical Inflammation

This study explores the role of NLRP3/T Cell Senescence in diabetes-mediated immune dysfunction to promote periapical inflammation. All experiments were carried out with approval from the Ethical Committee. We established models of type 2 diabetes mellitus, experimental apical periodontitis, and adoptive T cell transfer in male C57BL/6J mice. HE staining, immunohistochemical staining, RT-qPCR, ELISA, and flow cytometry were used to analyze T cell senescence characterization. microCT was used to analyze periapical lesions. Diabetic mice had increased NLRP3 expression and aggravated apical lesions, while thymic involution was exacerbated, and serum senescence-associated secretory phenotypes were increased. In spleen and cervical lymph nodes, the expression of NLRP3 and p16 was increased, the expression of CD27, the ratio of naive/memory T cells and the ratio of Trey/Th17 were decreased. These changes could be reversed with NLRP3 inhibitor MCC950 or adoptive young T cell transfer. It was confirmed that diabetes mellitus regulates T cell senescence through NLRP3, generating immune dysfunction, which in turn promotes periapical inflammation. And targeting NLRP3/T cell senescence will reverse the promotional effect of diabetes mellitus on periapical inflammation.