Involvement of macrophage-derived retinoids in the regulation of transglutaminase 2 expression and the phagocytosis enhancing effect of dexamethasone

Abstract

Rapid and effective clearance of apoptotic cells by phagocytes is essential for maintaining tissue homeostasis. Transglutaminase 2 (TG2) expressed both in apoptotic and engulfing cells ensures fast recognition and removal of apoptotic cells.T cells differentiate in the thymus, and during their selection processes 95% of the newly produced cells die and clear. For the in vivo induction of TG2 factors found in the thymic environment are required. We found that some of such factors are vitamin A derivatives, which are produced in macrophages engulfing apoptotic cells in a lipid sensing receptor-dependent manner. Retinoid produced by engulfing macrophages contribute to the TG2 expression in apoptotic thymocytes in vivo. We found that retinoids are also produced in macrophages exposed to a glucocorticoid hormone dexamethasone, which enhances the phagocytic capacity of macrophages. Retinoids were required for glucocorticoid-induced enhancement of long-term phagocytosis by promoting efficient upregulation of lipid sensing receptors, which can promote the rapid and early removal of dying cells.