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

Autor(es):Mostrar menos -

Santiago-Carvalho, Igor ; Almeida-Santos, Gislane ; Macedo, Bruna Gois ; Barbosa-Bomfim, Caio Cesar ; Almeida, Fabricio Moreira ; Cione, Marcos Vinicios Pinheiro ; Vardam-Kaur, Trupti ; Masuda, Mia ; Van Dijk, Sarah ; Melo, Bruno Marcel ; do Nascimento, Rogerio Silva ; Souza, Rebeka da Conceicao ; Peixoto-Rangel, Alba Lucinia ; Coutinho-Silva, Robson ; Hirata, Mario Hiroyuki ; Alves-Filho, Jose Carlos ; Alvarez, Jose Maria ; Lassounskaia, Elena ; da Silva, Henrique Borges ; D'Imperio-Lima, Maria Regina

• Tipo de documento: Artigo Científico
• Fonte: CELL REPORTS; v. 42, n. 11, p. 22-pg., 2023-11-15.

Resumo

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 hyper virulent 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. (AU)

• Processo FAPESP: 19/24700-8 - Papel do receptor P2X7 na resposta de células T CD4 parenquimais e intravasculares em modelo de Tuberculose Experimental Grave
• Beneficiário: Igor Santiago de Carvalho
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 15/20432-8 - Intervenção em vias de sinalização associadas ao reconhecimento de dano celular visando reduzir a patologia das formas graves de malária e tuberculose
• Beneficiário: Maria Regina D'Império Lima
• Modalidade de apoio: Auxílio à Pesquisa - Temático