T cell-specific P2RX7 favors lung parenchymal CD4+ T cell accumulation in response to severe lung infections
Year: 2023
Type: article
Abstract: ABSTRACT 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. GRAPHICAL ABSTRACT
Source: Cell Reports
Authors: Igor Santiago-Carvalho, Gislane Almeida-Santos, Bruna Gois Macedo, Caio Cesar Barbosa-Bomfim, Fabricio Moreira Almeida, Marcos Vinícios Pinheiro Cione, Trupti Vardam-Kaur, Mia Masuda, Sarah Van Dijk, Bruno Marcel Melo, Rogério Silva do Nascimento, Rebeka da Conceição Souza, Alba Lucínia Peixoto-Rangel, Robson Coutinho-Silva, Mario Hiroyuki Hirata, José Carlos Alves-Filho, José Maria Álvarez, Elena Lassounskaia, Henrique Borges da Silva, Maria Regina D’Império-Lima
Language: English
Subfield: Physiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,460
Awards: G295657101, G3041655236, DEFINING THE FUNCTION OF EXTRACELLULAR ATP SENSING FOR MEMORY CD8+ T CELL GENERATION AND LONGEVITY, G4402799499, G4539897318, Intervention in signaling pathways associated with the recognition of cellular damage to reduce the pathology of severe forms of malaria and tuberculosis, G5918521623, G5951912529, G779068073, G7942297873, G7990243368, Control of antiviral memory CD8+ T cell longevity by extracellular ATP sensing
OpenAlex ID: W4388702555