Vitamin A enhances in vitro Th2 development via retinoid X receptor pathway

Charles B. Stephensen, Reuven Rasooly, Xiaowen Jiang, Michael A. Ceddia, Casey T. Weaver, Roshantha A S Chandraratna, R. Patterson Bucy

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133 Scopus citations

Abstract

Vitamin A deficiency diminishes Th2-mediated Ab responses, and high-level dietary vitamin A or treatment with the vitamin A metabolite retinoic acid (RA) enhances such responses. To identify a potential mechanism(s) underlying this in vivo activity of vitamin A, we examined the effects of all-trans and 9-cis RA on development of Th1 and Th2 cell populations using in vitro stimulation of Ag-naive ThO cells from the DO11.10 TCR-transgenic mouse. Treatment with 9-cis, but not with all-trans RA, at primary stimulation strongly enhanced Th2 development. IL-4-neutralizing Ab blocked this activity, but IL-12- and IFN-γ-neutralizing Ab did not. Because 9-cis RA regulates gene transcription via either RA receptors or retinoid X receptors (RXRs), we tested the Th2-enhancing activities of the RXR- and RA receptor-selective agonists AGN194204 and 4-((E)-2 -(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid (TTNPB). AGN194204 strongly enhanced Th2 development, whereas TTNPB did not. This RXR agonist also enhanced Th2 development when purified, naive ThO cells (L-selectinhigh/CD4+) were stimulated with CD3 and CD28 Abs in the absence of APCs. During primary antigenic stimulation of naive ThO cells from DO11.10 mice, AGN194204 increased IL-4 and IL-5 production, decreased IFN-γ production, increased mRNA in responding T cells for genes involved in Th2 development (IL.4, GATA-3, and c-maf), and decreased mRNA for genes involved in Th1 development (IFN-γ, T-bet, and IL-12R). These data show that stimulation of the RXR pathway enhances Th2 development, perhaps by affecting the relative expression of pertinent transcription factors, cytokines, and cytokine receptors.

Original languageEnglish (US)
Pages (from-to)4495-4503
Number of pages9
JournalJournal of Immunology
Volume168
Issue number9
StatePublished - May 1 2002

ASJC Scopus subject areas

  • Immunology

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    Stephensen, C. B., Rasooly, R., Jiang, X., Ceddia, M. A., Weaver, C. T., Chandraratna, R. A. S., & Bucy, R. P. (2002). Vitamin A enhances in vitro Th2 development via retinoid X receptor pathway. Journal of Immunology, 168(9), 4495-4503.