Human Peripheral Blood Mononuclear Cells Express High Levels of the Vitamin a Transport Protein, Stimulated by Retinoic Acid 6 (P19-004-19)

Abstract

Abstract Objectives Stimulated by retinoic acid 6 (STRA6) was the first to be identified in a novel category of proteins, cytokine signaling transporters, due to its ability to function as both a cell surface receptor and a membrane protein that binds to retinol binding protein facilitating cellular uptake of retinol. Retinol is metabolized to all-trans retinoic acid which functions as a steroid hormone transcription factor ligand to regulate genes generally involved in cellular differentiation. The role of vitamin A, as all-trans retinoic acid, in immunity is well characterized, but the role of STRA6 in mediating cellular uptake of vitamin A in immune cells is not understood. The objective of this research was to characterize the expression of STRA6 on human peripheral blood mononuclear cell (PBMC) subsets. We hypothesized STRA6 would be expressed by all PBMC subsets, but at different intensities. Methods A convenience sample of volunteers were recruited and PBMC were isolated by density gradient centrifugation. Multicolor flow cytometry was used to identify PBMC subsets and expression of STRA6. Confocal microscopy was used to determine cellular location and lipid raft association of STRA6 on cell lines and isolated PBMC. Results All T cell, natural killer cell, monocyte, and dendritic cell subsets analyzed expressed STRA6. Expression of STRA6 (median fluorescence intensity) was higher on CD303+ and CD141+ dendritic cells compared to CD1c+ dendritic cells, CD8+ T cells compared to CD4+ T cells, CD14+/CD16+ and CD14+/CD16- monocytes compared to CD14-/CD16+ monocytes, and CD56-/CD16+ natural killer cells compared to both CD56+/CD16 variable and CD56-/CD16 dim natural killer cells. Expression was not significantly correlated with age, sex, or body composition. Confocal microscopy showed STRA6 was not associated with GM1 cholera toxin subunit B staining and therefore not associated with lipid raft structures. Conclusions These results provide preliminary data in which to target vitamin A signaling, through cellular uptake of retinol, in immune cells to improve immune homeostasis in diverse populations. Funding Sources Funding for this project was provided by internal university support.