Year: 2019
Type: dissertation
Study design: Observational Study
Abstract: Stimulated by retinoic acid 6 (STRA6) was the first protein 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. We also hypothesized STRA6 would be co-localized with the lipid raft. 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. All T cell, natural killer cell, monocyte, and dendritic cell subsets analyzed expressed STRA6. Median fluorescence intensity of STRA6 was higher on pDC dendritic cells compared to mDC2 and mDC1 dendritic cells, cytotoxic T lymphocytes compared to T helper lymphocytes, intermediate compared to nonclassical and classical monocytes, and cytokine natural killer cells compared to both cytotoxic and CD56-/CD16 dim natural killer cells. Age was the best predictive factor for STRA6 expression. Confocal microscopy showed STRA6 was not associated with GM1 cholera toxin subunit B staining and therefore not associated with lipid raft structures. 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. With further research and development, STRA6 signaling in immune cells may be a therapeutic target for immune mediated diseases.
Author: Crisha Brooks Barrett
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2964249394