Modulation of immune responses by bile acid receptor agonists in myasthenia gravis

J Neuroimmunol. 2020 Dec 15;349:577397. doi: 10.1016/j.jneuroim.2020.577397. Epub 2020 Sep 18.

Abstract

Bile acids bind to multiple receptors, including Takeda G protein-coupled receptor 5 (TGR5) and farnesoid-X-receptors alpha (FXRα). We compared the response of PBMCs to the activation of these receptors in healthy controls and myasthenic patients. We found that TGR5 is a more potent negative regulator of T cell cytokine response than FXRα in both groups. In contrast, TGR5 and FXRα agonists elicit distinct B cell responses in myasthenia compared to controls, specifically on the frequency of IL-6+ B cells and regulatory B cells, as well as IL-10 secretion from PBMCs. We propose that TGR5 is a potential therapeutic target in myasthenia.

Keywords: Autoimmune; Bile acids; Cytokines; Neuromuscular junction; Regulatory B cells; Regulatory T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cells, Cultured
  • Female
  • Humans
  • Immunity, Cellular / drug effects
  • Immunity, Cellular / immunology*
  • Immunologic Factors / pharmacology
  • Immunologic Factors / therapeutic use
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Male
  • Middle Aged
  • Myasthenia Gravis / drug therapy
  • Myasthenia Gravis / immunology*
  • Receptors, Cytoplasmic and Nuclear / agonists*
  • Receptors, Cytoplasmic and Nuclear / immunology*
  • Receptors, G-Protein-Coupled / agonists*
  • Receptors, G-Protein-Coupled / immunology*
  • Young Adult

Substances

  • GPBAR1 protein, human
  • Immunologic Factors
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, G-Protein-Coupled
  • farnesoid X-activated receptor