Vitamin D regulates cross talk between epithelial cells and immune cells through the secretion of CD14

Abstract

Inflammatory signaling between epithelial cells and immune cells contributes to a variety of diseases including cancer, autoimmune disorders, and obesity. Vitamin D, a potent immunomodulator, has been shown to regulate immune responses and reduce the risk of infections by acting on immune cells, yet its effects on the immune functions of epithelial cells and their impact on the immune microenvironment in epithelial tissues are less clear. We have demonstrated that 1α,25‐dihydroxyvitamin D (1,25D) dramatically increases the expression of the pattern recognition receptor CD14, which binds microbial lipopolysaccahride (LPS), in human mammary epithelial (HME) cells. We found through ELISA and microscopy that 1,25D enhances the accumulation of soluble not membrane‐localized CD14 and that conditioned media from 1,25D‐treated HME cells, which contains soluble CD14, promotes anti‐inflammatory responses from macrophages when exposed to LPS. Studies with the vitamin D receptor (VDR) analog JN, a non‐genomic VDR agonist, found JN induces CD14 expression and secretion comparable to 1,25D suggesting the membrane‐localized VDR contributes to 1,25D's induction of CD14. Overall this study supports the concept that 1,25D stimulates the secretion of CD14 from epithelial cells through the VDR to promote an anti‐inflammatory environment.Grant Funding Source: National Center for Complementary and Alternative Medicine Predoctoral F31 NRSA Fellowship