Cell-specific P2RX7 promotes the longevity of lung tissue-resident helper CD4 T cells in response to influenza infection

Abstract Development of universal influenza (flu) vaccines requires better knowledge lung-resident immune responses. That includes flu-specific CD4 T cells, which establish long-term lung residency and induce a diversified local protective response to subsequent infection. Tissue-resident helper (Trh) cells are subset that share phenotypic functional features with follicular (Tfh). Trh serve amplify responses, express high levels the extracellular ATP (eATP) sensor P2RX7. Considering eATP in increase flu infection, we used cell-specific P2RX7-knockout (KO) mice test role P2RX7 for cell responses flu. During acute phase found promotes accumulation inside tissue. Moreover, promoted this establishment via induction CXCR3 upregulation. Despite no specific defects pool at phase, P2RX7-KO led progressive decay cells. Consequently, lungs cell-P2RX7-KO had reduced B Our single-cell RNAseq showed expression survival mitochondrial genes findings suggest sensing by induces flu, impacting subsets. National Institute Allergy Infectious Diseases (NIAID) (H.BdS.: R00 AI139381, R01 AI170649).