Mechanism underlying the suppressor activity of retinoic acid on IL4-induced IgE synthesis and its physiological implication

Goo-Young Seo; Jeong-Min Lee; Young-Saeng Jang; Seung Goo Kang; Sung-Il Yoon; Hyun-Jeong Ko; Geun-Shik Lee; Seok-Rae Park; Cathryn R Nagler; Pyeung-Hyeun Kim

doi:10.1016/j.cellimm.2017.10.001

Mechanism underlying the suppressor activity of retinoic acid on IL4-induced IgE synthesis and its physiological implication

Cell Immunol. 2017 Dec:322:49-55. doi: 10.1016/j.cellimm.2017.10.001. Epub 2017 Oct 3.

Authors

Affiliations

¹ Department of Molecular Bioscience, School of Biomedical Science and Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon 24341, Republic of Korea; Department of Pathology and Committee on Immunology, The University of Chicago, 924 East 57th Street, R120, Chicago, IL 60637, USA.
² Department of Molecular Bioscience, School of Biomedical Science and Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon 24341, Republic of Korea.
³ Division of Biomedical Convergence, School of Biomedical Science and Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon 24341, Republic of Korea.
⁴ Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon 24341, Republic of Korea.
⁵ College of Veterinary Medicine, Kangwon National University, Chuncheon 24341, Republic of Korea.
⁶ Department of Microbiology, College of Medicine, Konyang University, Daejeon 35365, Republic of Korea.
⁷ Department of Pathology and Committee on Immunology, The University of Chicago, 924 East 57th Street, R120, Chicago, IL 60637, USA.
⁸ Department of Molecular Bioscience, School of Biomedical Science and Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon 24341, Republic of Korea. Electronic address: phkim@kangwon.ac.kr.

Abstract

The present study extends an earlier report that retinoic acid (RA) down-regulates IgE Ab synthesis in vitro. Here, we show the suppressive activity of RA on IgE production in vivo and its underlying mechanisms. We found that RA down-regulated IgE class switching recombination (CSR) mainly through RA receptor α (RARα). Additionally, RA inhibited histone acetylation of germ-line ε (GL ε) promoter, leading to suppression of IgE CSR. Consistently, serum IgE levels were substantially elevated in vitamin A-deficient (VAD) mice and this was more dramatic in VAD-lecithin:retinol acyltransferase deficient (LRAT^-/-) mice. Further, serum mouse mast cell protease-1 (mMCP-1) level was elevated while frequency of intestinal regulatory T cells (Tregs) were diminished in VAD LRAT^-/- mice, reflecting that deprivation of RA leads to allergic immune response. Taken together, our results reveal that RA has an IgE-repressive activity in vivo, which may ameliorate IgE-mediated allergic disease.

Keywords: CSR; Food allergy; IgE; RARα; Retinoic acid; Vitamin A deficient mice.

MeSH terms

Acyltransferases / deficiency
Acyltransferases / genetics
Animals
Chymases / metabolism
Food Hypersensitivity / drug therapy
Food Hypersensitivity / immunology
Immunoglobulin Class Switching / drug effects*
Immunoglobulin Class Switching / immunology
Immunoglobulin E / biosynthesis*
Immunoglobulin E / blood
Interleukin-4 / metabolism*
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Retinoic Acid Receptor alpha / immunology
T-Lymphocytes, Regulatory / immunology
Tretinoin / pharmacology*
Vitamin A / genetics
Vitamin A Deficiency / blood*
Vitamin A Deficiency / genetics

Substances

Retinoic Acid Receptor alpha
Vitamin A
Interleukin-4
Immunoglobulin E
Tretinoin
Acyltransferases
lecithin-retinol acyltransferase
Chymases
Mcpt1 protein, mouse

Grants and funding

R01 AI106302/AI/NIAID NIH HHS/United States