title: Essential role for retinoic acid in the promotion of CD4(+) T cell effector responses via retinoic acid receptor alpha.
abstract: Vitamin A and its metabolite, retinoic acid (RA) are implicated in the regulation of immune homeostasis via the peripheral induction of regulatory T cells. Here we showed RA was also required to elicit proinflammatory CD4(+) helper T cell responses to infection and mucosal vaccination. Retinoic acid receptor alpha (RARα) was the critical mediator of these effects. Antagonism of RAR signaling and deficiency in RARα (Rara(-/-)) resulted in a cell-autonomous CD4(+) T cell activation defect, which impaired intermediate signaling events, including calcium mobilization. Altogether, these findings reveal a fundamental role for the RA-RARα axis in the development of both regulatory and inflammatory arms of adaptive immunity and establish nutritional status as a broad regulator of adaptive T cell responses.
authors.affiliation: Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Hall
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Cannons
authors.forename: John R
authors.initials: JR
authors.lastname: Grainger
authors.forename: Liliane M
authors.initials: LM
authors.lastname: Dos Santos
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Hand
authors.forename: Shruti
authors.initials: S
authors.lastname: Naik
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Wohlfert
authors.forename: David B
authors.initials: DB
authors.lastname: Chou
authors.forename: Guillaume
authors.initials: G
authors.lastname: Oldenhove
authors.forename: Melody
authors.initials: M
authors.lastname: Robinson
authors.forename: Michael E
authors.initials: ME
authors.lastname: Grigg
authors.forename: Robin
authors.initials: R
authors.lastname: Kastenmayer
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Schwartzberg
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Belkaid
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006706:Homeostasis / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018168:Receptors, Retinoic Acid / Q000276:immunology*; D000072482:Retinoic Acid Receptor alpha; D015398:Signal Transduction; D014123:Toxoplasmosis / Q000276:immunology; D014212:Tretinoin / Q000276:immunology*
chemical_list: C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin