The Retinoic Acid Receptor-α mediates human T-cell activation and Th2 cytokine and chemokine production

Harry D Dawson¹ , Gary Collins² , Robert Pyle² , Michael Key² and Dennis D Taub²

¹Diet Genomics and Immunology Lab, United States Department of Agriculture, Beltsville, MD 20705, USA

²Laboratory of Immunology, Gerontology Research Center, National Institute on Aging, NIH, Baltimore, MD 21224, USA

author email corresponding author email

BMC Immunology 2008, 9:16doi:10.1186/1471-2172-9-16


Published:	16 April 2008

Abstract

Background

We have recently demonstrated that all-trans-retinoic acid (ATRA) and 9-cis-retinoic acid (9-cis RA) promote IL-4, IL-5 and IL-13 synthesis, while decreasing IFN-γ and TNF-α expression by activated human T cells and reduces the synthesis of IL-12p70 from accessory cells. Here, we have demonstrated that the observed effects using ATRA and 9-cis RA are shared with the clinically useful RAR ligand, 13-cis retinoic acid (13-cis RA), and the retinoic acid receptor-α (RAR-α)-selective agonist, AM580 but not with the RAR-β/γ ligand, 4-hydroxyphenylretinamide (4-HPR).

Results

The increase in type 2 cytokine production by these retinoids correlated with the expression of the T cell activation markers, CD69 and CD38. The RAR-α-selective agonist, AM580 recapitulated all of the T cell activation and type 2 cytokine-inducing effects of ATRA and 9-cis-RA, while the RAR-α-selective antagonist, RO 41–5253, inhibited these effects.

Conclusion

These results strongly support a role for RAR-α engagement in the regulation of genes and proteins involved with human T cell activation and type 2 cytokine production.