Scavenger Receptor class B type I is Required for 25‐Hydroxycholecalciferol Cellular Uptake and Signaling in Myeloid Cells

SCOPE Vitamin D3 is a critical molecule for the properly controlled activity of the immune system. In myeloid-derived cells, vitamin D3 induces the production of the antimicrobial and antitumor peptide cathelicidin. In this study, we explored the mechanism of entry of 25-hydroxycholecalciferol (25(OH)D) in myeloid-derived cells. METHODS AND RESULTS Here, we describe a novel regulatory pathway of vitamin D3 biology. Using a polyclonal antibody, two different chemical inhibitors, and high-density lipoprotein as a competing ligand, we demonstrate that the 25(OH)D signaling pathway in myeloid cells depends on scavenger receptor class B type I (SR-B1). This effect was observed in the THP-1 monocytic cell line and in human primary monocytes. SR-B1 blockade abrogates the cellular uptake of 25(OH)D leading to a general shut down of the gene transcription program modulated by 25(OH)D. The results obtained at the transcriptional level were confirmed at the protein and functional level for CD14 in the THP-1 cell line. CONCLUSION In conclusion, SR-B1 plays a critical role in vitamin D3 biology, paving the way for novel therapeutic interventions. This article is protected by copyright. All rights reserved.