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

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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

• Document type: Journal article
• Source: CELL REPORTS; v. 42, n. 11, p. 22-pg., 2023-11-15.

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 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)

• FAPESP's process: 19/24700-8 - Role of P2X7 receptor on parenchymal and intravascular CD4 T cell response in a Severe Experimental Tuberculosis model
• Grantee: Igor Santiago de Carvalho
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 15/20432-8 - Intervention in signaling pathways associated with the recognition of cellular damage to reduce the pathology of severe forms of malaria and tuberculosis
• Grantee: Maria Regina D'Império Lima
• Support Opportunities: Research Projects - Thematic Grants