HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Dzhagalov, I. Articles by He, Y.-W. Search for Related Content PubMed PubMed Citation Articles by Dzhagalov, I. Articles by He, Y.-W.

Regulation of CD8⁺ T Lymphocyte Effector Function and Macrophage Inflammatory Cytokine Production by Retinoic Acid Receptor ¹

Ivan Dzhagalov^*, Pierre Chambon and You-Wen He^2,*

^* Department of Immunology, Duke University Medical Center, Durham, NC 27710; and Institut de Genetique et de Biologie Moleculaire et Cellulaire, Centre National de la Recherche Scientifique-Institut National de la Santé et de la Recherche Médicale, Universite Louis Pasteur, Strasbourg, France

Vitamin A and its derivatives regulate a broad array of immune functions. The effects of these retinoids are mediated through members of retinoic acid receptors (RARs) and retinoid X receptors. However, the role of individual retinoid receptors in the pleiotropic effects of retinoids remains unclear. To dissect the role of these receptors in the immune system, we analyzed immune cell development and function in mice conditionally lacking RAR, the third member of the RAR family. We show that RAR is dispensable for T and B lymphocyte development, the humoral immune response to a T-dependent Ag and in vitro Th cell differentiation. However, RAR-deficient mice had a defective primary and memory CD8⁺ T cell response to Listeria monocytogenes infection. Unexpectedly, RAR-deficient macrophages exhibited impaired inflammatory cytokine production upon TLR stimulation. These results suggest that under physiological condition, RAR is a positive regulator of inflammatory cytokine production.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grant CA92123.

² Address correspondence and reprint requests to Dr. You-Wen He, Box 3010, Duke University Medical Center, Durham, NC 27710. E-mail address: he000004{at}mc.duke.edu

³ Abbreviations used in this paper: ATRA, all-trans retinoic acid; 9-cis-RA, 9-cis-retinoic acid; BM, bone marrow; Cre, cAMP response element; DC, dendritic cell; DN, double negative; DP, double positive; GBS, group B streptococcus; hIL, human IL; HPRT, hypoxanthine phosphoribosyltransferase; IEL, intraepithelial lymphocyte; KLH, keyhole limpet hemocyanin; PGN, peptidoglycan; PPAR, peroxisome proliferator-activated receptor; RAR, retinoic acid receptor; rLmOVA, recombinant Listeria monocytogenes strain secreting chicken OVA; RXR, retinoid X receptor; SP, single positive; LXR, liver X receptor.