CXCR2 deficiency impairs auditory function in spiral ganglion neurons by altering excitability

Abstract CXC chemokine receptor 2 (CXCR2), a key member of the chemokine receptor family, plays a central role in regulating immune and inflammatory responses. Inflammation has been established as a critical pathological factor in various auditory disorders, including noise-induced hearing loss, drug-induced ototoxicity, and age-related hearing loss; however, the expression patterns and biological functions of CXCR2 in key cells involved in auditory signal transduction remain unclear. Here, we demonstrated that CXCR2 is abundantly expressed in cochlear spiral ganglion neurons (SGNs), hair cells, and the stria vascularis. Genetic deletion of CXCR2 resulted in progressive hearing loss in mice. SGNs from CXCR2 knockout mice exhibited increased expression of the Kv1.2 potassium channel, impaired ribbon synapses, and altered myelin integrity. Electrophysiological analysis revealed enhanced Kv1 currents and significantly reduced excitability in CXCR2-deficient SGNs. Notably, CXCR2 knockdown in SGNs using an adeno-associated virus recapitulated the hearing loss phenotype. In conclusion, our findings revealed that CXCR2 is essential for hearing as it regulates SGN excitability.