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.

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