Pleiotropic immunoregulation by bile acids in pathophysiology

Area of Science:

• Immunology
• Metabolism
• Microbiology

Background:

• Bile acids (BAs) have expanded roles beyond digestion to act as crucial signaling molecules.
• BAs integrate host metabolism, gut microbiota, and immune system functions.
• Dysregulated BA signaling is implicated in various diseases, including inflammatory, autoimmune, metabolic, and malignant conditions.

Purpose of the Study:

• To review the multifaceted roles of bile acids in regulating innate and adaptive immunity.
• To examine the mechanisms by which bile acids modulate immune cell activity through specific receptors.
• To discuss the implications of bile acid signaling in different tissues and disease contexts.

Main Methods:

• Literature review of studies on bile acid signaling and immune function.
• Analysis of the roles of specific receptors (FXR, TGR5, VDR, RORs) in mediating BA effects on immune cells.
• Examination of tissue-specific BA signaling and its impact on immune homeostasis.

Main Results:

• Bile acids modulate the activity of key immune cells, including macrophages, dendritic cells, T cells, NK cells, and NKT cells.
• Specific receptors like FXR, TGR5, VDR, and RORs mediate diverse immune-regulatory functions of BAs.
• Tissue-specific BA signaling influences immune homeostasis in the gut, liver, CNS, and tumor microenvironment.

Conclusions:

• Bile acids are critical regulators of immune homeostasis and play a significant role in health and disease.
• Targeting bile acid pathways offers promising therapeutic strategies for immune-related disorders.
• Further research into bile acid-immune crosstalk can advance precision immunotherapy and microbiome-based interventions.