An extra-nasal olfactory GPCR–carbonyl axis drives cytokine storms in sepsis

In this study, we investigated the role of the extra-nasal olfactory receptor Or5v1/1b as a chemosensory GPCR that amplifies innate immune signaling and systemic inflammation. Reactive carbonyl metabolites generated during inflammation, including hexanal, activate Or5v1/1b and enhance Toll-like receptor-mediated inflammatory responses through cAMP/Ca2+–NF-κB signaling.

Genetic ablation of Or5v1/1b protects mice from LPS-induced sepsis by suppressing systemic inflammatory responses and organ damage. RNA sequencing was performed to characterize Or5v1/1b-dependent transcriptional responses in peritoneal macrophages and lung tissues from wild-type and Or5v1/1b-deficient mice under untreated and LPS-stimulated conditions. These transcriptomic data provide insight into the molecular mechanisms by which Or5v1/1b links inflammatory tissue stress to innate immune activation and systemic inflammation.