Vitamin D Homeostasis in Sarcoidosis

Sarcoidosis is a multi‐system inflammatory disease characterized by T‐helper lymphocyte hyperactivity leading to granulomatous inflammation. The granuloma cells autonomously convert 25‐hydroxy‐vitamin‐D (25OHD) to the active metabolite 1,25‐dihydroxy‐vitamin‐D (1,25OH2D) independent of normal feedback control but dependent on substrate (25OHD) concentration. Circulating 1,25OH2D exerts both anti‐inflammatory and mineral metabolic actions. Deficiency of 25OHD limits substrate‐dependent 1,25OH2D synthesis, diminishes anti‐antigenic innate immunity and augments pro‐inflammatory adaptive immunity. Thus, low vitamin‐D stores could aggravate sarcoid inflammation while repletion of vitamin‐D stores could mitigate inflammation in sarcoidosis.