title: To investigate the necessity of STRA6 upregulation in T cells during T cell immune responses.
abstract: 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.
authors.affiliation: Laboratoire d'immunologie, Centre de recherche, Centre hospitalier de l'Université de Montréal (CRCHUM) - Hôpital Notre-Dame, Montréal, Québec, Canada.
authors.forename: Rafik
authors.initials: R
authors.lastname: Terra
authors.affiliation: Laboratoire d'immunologie, Centre de recherche, Centre hospitalier de l'Université de Montréal (CRCHUM) - Hôpital Notre-Dame, Montréal, Québec, Canada.
authors.forename: Xuehai
authors.initials: X
authors.lastname: Wang
authors.affiliation: Laboratoire d'immunologie, Centre de recherche, Centre hospitalier de l'Université de Montréal (CRCHUM) - Hôpital Notre-Dame, Montréal, Québec, Canada.
authors.forename: Yan
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Institut national de la recherche scientifique (INRS) - Institut Armand-Frappier, Laval, Québec, Canada.
authors.forename: Tania
authors.initials: T
authors.lastname: Charpentier
authors.affiliation: Institut national de la recherche scientifique (INRS) - Institut Armand-Frappier, Laval, Québec, Canada.
authors.forename: Alain
authors.initials: A
authors.lastname: Lamarre
authors.affiliation: Department of Physiology, Jules Stein Eye Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhong
authors.affiliation: Department of Physiology, Jules Stein Eye Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.affiliation: Laboratoire d'immunologie, Centre de recherche, Centre hospitalier de l'Université de Montréal (CRCHUM) - Hôpital Notre-Dame, Montréal, Québec, Canada.
authors.forename: Jianning
authors.initials: J
authors.lastname: Mao
authors.affiliation: Laboratoire d'immunologie, Centre de recherche, Centre hospitalier de l'Université de Montréal (CRCHUM) - Hôpital Notre-Dame, Montréal, Québec, Canada.
authors.forename: Shijie
authors.initials: S
authors.lastname: Qi
authors.affiliation: Laboratoire d'immunologie, Centre de recherche, Centre hospitalier de l'Université de Montréal (CRCHUM) - Hôpital Notre-Dame, Montréal, Québec, Canada.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Luo
authors.affiliation: Laboratoire d'immunologie, Centre de recherche, Centre hospitalier de l'Université de Montréal (CRCHUM) - Hôpital Notre-Dame, Montréal, Québec, Canada ; Service de néphrologie, Centre de recherche, Centre hospitalier de l'Université de Montréal (CRCHUM) - Hôpital Notre-Dame, Montréal, Québec, Canada.
authors.forename: Jiangping
authors.initials: J
authors.lastname: Wu
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D005123:Eye / Q000276:immunology / Q000378:metabolism; D005260:Female; D007111:Immunity, Cellular; D008213:Lymphocyte Activation; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D015854:Up-Regulation; D014801:Vitamin A / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; C108001:Stra6 protein, mouse; D014801:Vitamin A