Bile acid-activated receptors in innate and adaptive immunity: targeted drugs and biological agents

Eur J Immunol. 2023 Aug;53(8):e2250299. doi: 10.1002/eji.202250299. Epub 2023 Jun 23.

Abstract

Bile acid-activated receptors (BARs) such as a G-protein bile acid receptor 1 and the farnesol X receptor are activated by bile acids (BAs) and have been implicated in the regulation of microbiota-host immunity in the intestine. The mechanistic roles of these receptors in immune signaling suggest that they may also influence the development of metabolic disorders. In this perspective, we provide a summary of recent literature describing the main regulatory pathways and mechanisms of BARs and how they affect both innate and adaptive immune system, cell proliferation, and signaling in the context of inflammatory diseases. We also discuss new approaches for therapy and summarize clinical projects on BAs for the treatment of diseases. In parallel, some drugs that are classically used for other therapeutic purposes and BAR activity have recently been proposed as regulators of immune cells phenotype. Another strategy consists of using specific strains of gut bacteria to regulate BA production in the intestine.

Keywords: Bile acid; FXR; GPBAR1; Intestinal macrophage; ROR-γ.

Publication types

  • Review