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To Investigate the Necessity of STRA6 Upregulation in T Cells during T Cell Immune Responses
Our earlier study revealed that STRA6 (stimulated by retinoic acid gene 6) was up-regulated within 3 h of TCR stimulation. STRA6 is the high-affinity receptor for plasma retinol-binding protein (RBP) and mediates cellular vitamin A uptake. We generated STRA6 knockout (KO) mice to assess whether such...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3876989/ https://www.ncbi.nlm.nih.gov/pubmed/24391722 http://dx.doi.org/10.1371/journal.pone.0082808 |
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author | Terra, Rafik Wang, Xuehai Hu, Yan Charpentier, Tania Lamarre, Alain Zhong, Ming Sun, Hui Mao, Jianning Qi, Shijie Luo, Hongyu Wu, Jiangping |
author_facet | Terra, Rafik Wang, Xuehai Hu, Yan Charpentier, Tania Lamarre, Alain Zhong, Ming Sun, Hui Mao, Jianning Qi, Shijie Luo, Hongyu Wu, Jiangping |
author_sort | Terra, Rafik |
collection | PubMed |
description | Our earlier study revealed that STRA6 (stimulated by retinoic acid gene 6) was up-regulated within 3 h of TCR stimulation. STRA6 is the high-affinity receptor for plasma retinol-binding protein (RBP) and mediates cellular vitamin A uptake. We generated STRA6 knockout (KO) mice to assess whether such up-regulation was critical for T-cell activation, differentiation and function. STRA6 KO mice under vitamin A sufficient conditions were fertile without apparent anomalies upon visual inspection. The size, cellularity and lymphocyte subpopulations of STRA6 KO thymus and spleen were comparable to those of their wild type (WT) controls. KO and WT T cells were similar in terms of TCR-stimulated proliferation in vitro and homeostatic expansion in vivo. Naive KO CD4 cells differentiated in vitro into Th1, Th2, Th17 as well as regulatory T cells in an analogous manner as their WT counterparts. In vivo experiments revealed that anti-viral immune responses to lymphocytic choriomeningitis virus in KO mice were comparable to those of WT controls. We also demonstrated that STRA6 KO and WT mice had similar glucose tolerance. Total vitamin A levels are dramatically lower in the eyes of KO mice as compared to those of WT mice, but the levels in other organs were not significantly affected after STRA6 deletion under vitamin A sufficient conditions, indicating that the eye is the mouse organ most sensitive to the loss of STRA6. Our results demonstrate that 1) in vitamin A sufficiency, the deletion of STRA6 in T cells does no affect the T-cell immune responses so-far tested, including those depend on STAT5 signaling; 2) STRA6-independent vitamin A uptake compensated the lack of STRA6 in lymphoid organs under vitamin A sufficient conditions in mice; 3) STRA6 is critical for vitamin A uptake in the eyes even in vitamin A sufficiency. |
format | Online Article Text |
id | pubmed-3876989 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38769892014-01-03 To Investigate the Necessity of STRA6 Upregulation in T Cells during T Cell Immune Responses Terra, Rafik Wang, Xuehai Hu, Yan Charpentier, Tania Lamarre, Alain Zhong, Ming Sun, Hui Mao, Jianning Qi, Shijie Luo, Hongyu Wu, Jiangping PLoS One Research Article Our earlier study revealed that STRA6 (stimulated by retinoic acid gene 6) was up-regulated within 3 h of TCR stimulation. STRA6 is the high-affinity receptor for plasma retinol-binding protein (RBP) and mediates cellular vitamin A uptake. We generated STRA6 knockout (KO) mice to assess whether such up-regulation was critical for T-cell activation, differentiation and function. STRA6 KO mice under vitamin A sufficient conditions were fertile without apparent anomalies upon visual inspection. The size, cellularity and lymphocyte subpopulations of STRA6 KO thymus and spleen were comparable to those of their wild type (WT) controls. KO and WT T cells were similar in terms of TCR-stimulated proliferation in vitro and homeostatic expansion in vivo. Naive KO CD4 cells differentiated in vitro into Th1, Th2, Th17 as well as regulatory T cells in an analogous manner as their WT counterparts. In vivo experiments revealed that anti-viral immune responses to lymphocytic choriomeningitis virus in KO mice were comparable to those of WT controls. We also demonstrated that STRA6 KO and WT mice had similar glucose tolerance. Total vitamin A levels are dramatically lower in the eyes of KO mice as compared to those of WT mice, but the levels in other organs were not significantly affected after STRA6 deletion under vitamin A sufficient conditions, indicating that the eye is the mouse organ most sensitive to the loss of STRA6. Our results demonstrate that 1) in vitamin A sufficiency, the deletion of STRA6 in T cells does no affect the T-cell immune responses so-far tested, including those depend on STAT5 signaling; 2) STRA6-independent vitamin A uptake compensated the lack of STRA6 in lymphoid organs under vitamin A sufficient conditions in mice; 3) STRA6 is critical for vitamin A uptake in the eyes even in vitamin A sufficiency. Public Library of Science 2013-12-31 /pmc/articles/PMC3876989/ /pubmed/24391722 http://dx.doi.org/10.1371/journal.pone.0082808 Text en © 2013 Terra et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Terra, Rafik Wang, Xuehai Hu, Yan Charpentier, Tania Lamarre, Alain Zhong, Ming Sun, Hui Mao, Jianning Qi, Shijie Luo, Hongyu Wu, Jiangping To Investigate the Necessity of STRA6 Upregulation in T Cells during T Cell Immune Responses |
title | To Investigate the Necessity of STRA6 Upregulation in T Cells during T Cell Immune Responses |
title_full | To Investigate the Necessity of STRA6 Upregulation in T Cells during T Cell Immune Responses |
title_fullStr | To Investigate the Necessity of STRA6 Upregulation in T Cells during T Cell Immune Responses |
title_full_unstemmed | To Investigate the Necessity of STRA6 Upregulation in T Cells during T Cell Immune Responses |
title_short | To Investigate the Necessity of STRA6 Upregulation in T Cells during T Cell Immune Responses |
title_sort | to investigate the necessity of stra6 upregulation in t cells during t cell immune responses |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3876989/ https://www.ncbi.nlm.nih.gov/pubmed/24391722 http://dx.doi.org/10.1371/journal.pone.0082808 |
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