The Regulatory Mechanisms of Indole-3-Carboxaldehyde in Immune Cells and Its Role in Autoimmune Diseases

Immune cells play a central role in the pathogenesis and progression of autoimmune diseases. Recent evidence indicates that metabolites produced by the gut microbiota are essential for maintaining immune cell homeostasis. Indole-3-carboxaldehyde (IAld), a key gut microbial metabolite, has garnered considerable attention due to its immunomodulatory properties in autoimmune diseases. In multiple sclerosis, IAld alleviates inflammation through modulation of mast cells and astrocytes; in rheumatoid arthritis (RA), IAld suppresses macrophage-mediated inflammation while concurrently promoting angiogenesis and osteoclastogenesis; in inflammatory bowel disease (IBD), IAld confers protection through reducing inflammatory responses, promoting intestinal barrier repair, and modulating the gut microbiota composition. IAld mediates its immunomodulatory effects by directly or indirectly modulating immune cell function, including secretion and regulatory activity (including neutrophils, macrophages, innate lymphoid cells, T cells, and others) via the aryl hydrocarbon receptor (AhR) signaling pathway. In this review, we summarize the mechanisms by which IAld acts on immune cells and discuss its implications for autoimmune disease pathogenesis. Finally, we outline current challenges in this field and provide a perspective on future research priorities.