Senescence-like cells recruit γδ T cells to drive prolonged hyposmia after SARS-CoV-2 infection in mice

ABSTRACT: Persistent hyposmia is a hallmark of post COVID-19 conditions, yet the mechanisms sustaining olfactory dysfunction after viral clearance remain poorly understood. Here, using mouse models of SARS-CoV-2 infection, we show that virus-induced senescence-like changes in uninfected olfactory mucosal fibroblasts persist long after viral clearance and drive prolonged olfactory dysfunction. These senescence-like cells secrete SASP factors, including IFNγ, CXCL9, and CXCL11, thereby recruiting γδ T cells to the olfactory mucosa. The accumulated γδ T cells produce excessive IL-17A, which acts on IL-17 receptor A expressed on olfactory sensory neurons, leading to sustained impairment of their function. Genetic ablation of senescence pathways (p16/p21 double knockout), pharmacological elimination of s

SUBMITTER: Shunya Tsuji 

PROVIDER: S-SCDT-10_1038-S44319-026-00769-6 | biostudies-other |

REPOSITORIES: biostudies-other