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Expression and Regulation of Nuclear Retinoic Acid Receptors in Human Lymphoid Cells

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Abstract

Retinoids are known to play an important role in cellular growth and differentiation and more recently in the immune response. Our laboratory has previously shown that all-trans-retinoic acid (atRA) augments immunoglobulin synthesis of cord blood mononuclear cells by enhancing the synthesis of certain cytokines. Transcriptional regulatory elements, the retinoic acid nuclear receptors (RAR), could mediate the RA-induced regulation of genes, e.g., cytokines whose products are involved in the pathways of immunoglobulin synthesis. Although much is known about RAR in various animal species and tissues, little is known about the expression of RAR and its isotypes in human lymphoid cells. In this study, we examined the RAR isotypes (RAR-α, RAR-β, RAR-γ) and their respective isoforms in T- and B-lymphoid cells using a quantitative RT-PCR assay. RAR-α1 and -γ1 were both constitutively expressed and did not change with the addition of atRA to human T- and B-cell lines or adenoidal T and B lymphocytes. In contrast, RAR-β2 was not detected. The addition of atRA to cell culture produced a marked increase in the amounts of RAR-β2 mRNA (2.2- to 41-fold). As with the RAR-β2 isoform, the addition of atRA increased RAR-α2 mRNA levels (3.4- to 17-fold), but only in EBV-transformed B cells and adenoidal B lymphocytes. The RAR-β1 and -β3 isoforms were undetectable in lymphoid cells and not inducible with atRA. RAR-γ2 was expressed at very low levels and was not inducible with atRA. Our results suggest that the expressions of the RAR-α2 and -β2 isoforms in lymphoid cells are highly controlled by atRA. Differences in the regulation of RAR isoforms by atRA in human lymphoid cells may be an important factor in the modulation of cytokine production and the augmentation in Ig synthesis by atRA.

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Authors and Affiliations

  1. Division of Allergy/Immunology and Pediatric, Rheumatology, Department of Pediatrics, Children's Hospital of Buffalo, SUNY Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York, 14222

    Mark Ballow & Cheryl Allen

  2. Children's Hospital, Medical Center of Fudan University, Shanghai, P.R. China

    Xiaochuan Wang & Shunan Xiang

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  1. Mark Ballow
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Ballow, M., Wang, X., Xiang, S. et al. Expression and Regulation of Nuclear Retinoic Acid Receptors in Human Lymphoid Cells. J Clin Immunol 23, 46–54 (2003). https://doi.org/10.1023/A:1021900331580

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