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

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-gamma and TNF-alpha 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-alpha (RAR-alpha)-selective agonist, AM580 but not with the RAR-beta/gamma 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-alpha-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-alpha-selective antagonist, RO 41-5253, inhibited these effects. CONCLUSION:These results strongly support a role for RAR-alpha engagement in the regulation of genes and proteins involved with human T cell activation and type 2 cytokine production.

journal_name

BMC Immunol

journal_title

BMC immunology

authors

Dawson HD,Collins G,Pyle R,Key M,Taub DD

doi

10.1186/1471-2172-9-16

subject

Has Abstract

pub_date

2008-04-16 00:00:00

pages

16

issn

1471-2172

pii

1471-2172-9-16

journal_volume

9

pub_type

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