The roles of transient receptor potential vanilloid in autoimmune diseases

Abstract

The transient receptor potential vanilloid (TRPV) is a family of tetrameric cation channels, expressed in various tissues and cell types. It includes thermosensitive isoforms (TRPV1–4) and calcium-permeable members (TRPV5–6). In the context of autoimmune diseases, TRPV channels have been firmly established as pivotal regulators that bridge changes in the cellular environment to the immune system.

Originally identified for their roles in thermosensation and nociception, these polymodal sensors have now emerged as crucial determinants of immune cell function. They are capable of converting chemical signals, temperature fluctuations, and mechanical forces into calcium-mediated signal transduction pathways. Mounting evidence indicates that dysregulated TRPV channel activity leads to pathological calcium influx, triggering a signaling cascade that reprograms the functions of key immune cells and modulates pain and itch signaling through neuroimmune crosstalk. These cascades amplify inflammatory responses, exacerbate autoimmune pathology, promote inflammatory cytokine release, and modulate pain/itch signaling via neuroimmune crosstalk.

Specifically, these mechanisms are instrumental in the progression including autoimmune disorders, such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), multiple sclerosis (MS), psoriasis, and atopic dermatitis (AD). Novel therapeutic strategies are emerging, aiming to modulate TRPV activity in autoimmune conditions. Approaches include suppressing hyperactive channels and leveraging their immunoregulatory potential. Promising preclinical results have highlighted that TRPV channels exhibit dual translational potential in mechanistic research of autoimmune diseases, integrating precise targeting with dynamic monitoring capabilities. However, translating these findings into clinical applications faces significant challenges, including differential effects on neuronal and immune signaling, as well as systemic side effects caused by disruptions to physiological homeostasis.

This narrative review discuss how TRPV channel signaling has enhanced our understanding of autoimmune disease initiation. By dissecting how TRPV-mediated immune dysregulation drives pathological immune responses, we seek to offer novel mechanistic insights to inform the development of more effective and comprehensive treatment strategies for autoimmune diseases.