RT Journal Article SR Electronic T1 T cell-specific P2RX7 favors lung parenchymal CD4+ T cell accumulation in response to severe lung infections JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.09.19.508603 DO 10.1101/2022.09.19.508603 A1 Igor Santiago-Carvalho A1 Gislane Almeida-Santos A1 Bruna Gois Macedo A1 Caio Cesar Barbosa-Bomfim A1 Fabricio Moreira Almeida A1 Marcos Vinícios Pinheiro Cione A1 Trupti Vardam-Kaur A1 Mia Masuda A1 Sarah Van Dijk A1 Bruno Marcel Melo A1 Rogério Silva do Nascimento A1 Rebeka da Conceição Souza A1 Alba Lucínia Peixoto-Rangel A1 Robson Coutinho-Silva A1 Mario H. Hirata A1 José Carlos Alves-Filho A1 José Maria Álvarez A1 Elena Lassounskaia A1 Henrique Borges da Silva A1 Maria Regina D’Império-Lima YR 2022 UL http://biorxiv.org/content/early/2022/09/19/2022.09.19.508603.abstract AB CD4+ T cells are key components of the immune response during lung infections and can mediate protection against tuberculosis (TB) or influenza. However, CD4+ T cells can also promote lung pathology during these infections, making it unclear how these cells control such discrepant effects. Using mouse models of hypervirulent TB and influenza, we observed that exaggerated accumulation of parenchymal CD4+ T cells promotes lung damage. Low numbers of lung CD4+ T cells, in contrast, are sufficient to protect against hypervirulent TB. In both situations, lung CD4+ T cell accumulation is mediated by CD4+ T cell-specific expression of the extracellular ATP (eATP) receptor P2RX7. P2RX7 upregulation in lung CD4+ T cells promotes expression of the chemokine receptor CXCR3 and favors in situ proliferation. Our findings suggest that direct sensing of lung eATP by CD4+ T cells is critical to induce tissue CD4+ T cell accumulation and pathology during lung infections.Competing Interest StatementH.BdS. is an advisor for International Genomics Consortium. The remaining authors do not have any competing interests.