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

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

doi:10.1016/j.celrep.2023.113448

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

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

Allergy, Asthma and Clinical Immunology

Research output: Contribution to journal › Article › peer-review

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 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.

Original language	English (US)
Article number	113448
Journal	Cell reports
Volume	42
Issue number	11
DOIs	https://doi.org/10.1016/j.celrep.2023.113448
State	Published - Nov 28 2023

Keywords

CD4 T cell
CP: Immunology
CXCR3
extracellular ATP
influenza
lung
lung damage
P2RX7
tuberculosis

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

Access to Document

10.1016/j.celrep.2023.113448

Cite this

Santiago-Carvalho, I., Almeida-Santos, G., Macedo, B. G., Barbosa-Bomfim, C. C., Almeida, F. M., Pinheiro Cione, M. V., Vardam-Kaur, T., Masuda, M., Van Dijk, S., Melo, B. M., Silva do Nascimento, R., da Conceição Souza, R., Peixoto-Rangel, A. L., Coutinho-Silva, R., Hirata, M. H., Alves-Filho, J. C., Álvarez, J. M., Lassounskaia, E., Borges da Silva, H., & D'Império-Lima, M. R. (2023). T cell-specific P2RX7 favors lung parenchymal CD4⁺ T cell accumulation in response to severe lung infections. Cell reports, 42(11), Article 113448. https://doi.org/10.1016/j.celrep.2023.113448

Santiago-Carvalho, I, Almeida-Santos, G, Macedo, BG, Barbosa-Bomfim, CC, Almeida, FM, Pinheiro Cione, MV, Vardam-Kaur, T, Masuda, M, Van Dijk, S, Melo, BM, Silva do Nascimento, R, da Conceição Souza, R, Peixoto-Rangel, AL, Coutinho-Silva, R, Hirata, MH, Alves-Filho, JC, Álvarez, JM, Lassounskaia, E, Borges da Silva, H & D'Império-Lima, MR 2023, 'T cell-specific P2RX7 favors lung parenchymal CD4⁺ T cell accumulation in response to severe lung infections', Cell reports, vol. 42, no. 11, 113448. https://doi.org/10.1016/j.celrep.2023.113448

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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 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.",

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AU - Santiago-Carvalho, Igor

AU - Almeida-Santos, Gislane

AU - Macedo, Bruna Gois

AU - Barbosa-Bomfim, Caio Cesar

AU - Almeida, Fabricio Moreira

AU - Pinheiro Cione, Marcos Vinícios

AU - Vardam-Kaur, Trupti

AU - Masuda, Mia

AU - Van Dijk, Sarah

AU - Melo, Bruno Marcel

AU - Silva do Nascimento, Rogério

AU - da Conceição Souza, Rebeka

AU - Peixoto-Rangel, Alba Lucínia

AU - Coutinho-Silva, Robson

AU - Hirata, Mario Hiroyuki

AU - Alves-Filho, José Carlos

AU - Álvarez, José Maria

AU - Lassounskaia, Elena

AU - Borges da Silva, Henrique

AU - D'Império-Lima, Maria Regina

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