TRPV4-Mast Cell Interactions in Neurogenic Inflammation and Chronic Diseases: A Narrative Review.

Transient receptor potential vanilloid 4 (TRPV4) is a polymodal cation channel that is widely expressed in sensory neurons, immune cells, and structural tissues, where it integrates mechanical, osmotic, and chemical stimuli to regulate both physiological responses and disease-associated signaling. Mast cells (MCs), key immune effector cells capable of rapid mediator release through degranulation, also express TRPV4. Increasing evidence supports TRPV4-MC signaling as an important neuroimmune interface, linking mechanical and inflammatory stimuli to tissue hypersensitivity and pain. In this review, we synthesize current evidence supporting a role for TRPV4 in MC-associated neuroimmune signaling across multiple disease contexts while distinguishing settings in which TRPV4 directly regulates MC activation from those in which MC responses arise through multicellular tissue interactions. Direct TRPV4-dependent MC activation has been described in conditions such as LL-37-driven rosacea and mechanically induced inflammation, whereas in disorders including asthma, visceral hypersensitivity, bladder pain syndromes, and osteoarthritis, TRPV4 activity in epithelial, neuronal, or stromal compartments more often influences MC function indirectly through ATP-purinergic signaling, cytokine release, and neuropeptide-mediated crosstalk. Across systems, TRPV4 emerges not as a single pathogenic switch but as part of a context-dependent signaling network whose functional consequences depend on cell type, tissue microenvironment, and disease stage. Altogether, these findings identify TRPV4 as a therapeutically actionable node within neuroimmune signaling pathways and support the development of tissue-specific and combination strategies targeting both TRPV4 activity and MC-mediated signaling in chronic inflammatory and pain disorders.

Duke Scholars

Author Soman Ninan Abraham Pathology

Author Carlene D Moore Neurology, Translational Brain Sciences