Details

Autor(en) / Beteiligte

• Santiago-Carvalho, Igor
• Almeida-Santos, Gislane
• Macedo, Bruna Gois
• Barbosa-Bomfim, Caio Cesar
• Almeida, Fabricio Moreira
• Pinheiro Cione, Marcos Vinícios
• Vardam-Kaur, Trupti
• Masuda, Mia
• Van Dijk, Sarah
• Melo, Bruno Marcel
• Silva do Nascimento, Rogério
• da Conceição Souza, Rebeka
• Peixoto-Rangel, Alba Lucínia
• Coutinho-Silva, Robson
• Hirata, Mario Hiroyuki
• Alves-Filho, José Carlos
• Álvarez, José Maria
• Lassounskaia, Elena
• Borges da Silva, Henrique
• D’Império-Lima, Maria Regina

Titel

T cell-specific P2RX7 favors lung parenchymal CD4+ T cell accumulation in response to severe lung infections

Ist Teil von

• Cell reports (Cambridge), 2023-11, Vol.42 (11), p.113448-113448, Article 113448

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2023

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 observe 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, favoring parenchymal CD4+ T cell accumulation. 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. [Display omitted] •eATP sensing via P2RX7 promotes lung CD4+ T cell residency in response to infection•P2RX7-induced lung CD4+ T cells lead to tissue pathology and poor host survival•P2RX7 induces lung CD4+ T cell establishment through CXCR3 expression Santiago-Carvalho et al. demonstrate that, in response to severe lung infections, sensing of extracellular ATP through P2RX7 leads to exacerbated numbers of lung parenchymal CD4+ T cells that promote pathology and impair host survival. Their results suggest a possible explanation for how tissue danger signals can inadvertently support pathogenic lung immune responses.