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Targeting chronic COVID-19 lung injury; Tofacitinib can be used against tissue-resident memory T cells.

ABSTRACT: Post-Covid pulmonary fibrosis is evident following severe COVID-19. There is an urgent need to identify the cellular and pathophysiological characteristics of chronic lung squeals of Covid-19 for the development of future preventive and/or therapeutic interventions. Tissue-resident memory T (T_RM) cells can mediate local immune protection against infections and cancer. Less beneficially, lung T_RM cells cause chronic airway inflammation and fibrosis by stimulating pathologic inflammation. The effects of Janus kinase (JAK), an inducer pathway of cytokine storm, inhibition on acute Covid-19 cases have been previously evaluated. Here, we propose that Tofacitinib by targeting the CD8⁺ T_RM cells could be a potential candidate for the treatment of chronic lung diseases induced by acute SARS-CoV-2 infection.

SUBMITTER: Zununi Vahed S

PROVIDER: S-EPMC8723825 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Targeting chronic COVID-19 lung injury; Tofacitinib can be used against tissue-resident memory T cells.

Zununi Vahed Sepideh S Hosseiniyan Khatibi Seyed Mahdi SM Ahmadian Elham E Ardalan Mohammadreza M

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 20220104

Post-Covid pulmonary fibrosis is evident following severe COVID-19. There is an urgent need to identify the cellular and pathophysiological characteristics of chronic lung squeals of Covid-19 for the development of future preventive and/or therapeutic interventions. Tissue-resident memory T (T<sub>RM</sub>) cells can mediate local immune protection against infections and cancer. Less beneficially, lung T<sub>RM</sub> cells cause chronic airway inflammation and fibrosis by stimulating pathologic ...[more]

PMID: 34995938

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Project description:Mycobacterium bovis Bacille Calmette-Guérin (BCG) is the only licensed vaccine against tuberculosis (TB), yet its moderate efficacy against pulmonary TB calls for improved vaccination strategies. Mucosal BCG vaccination generates superior protection against TB in animal models; however, the mechanisms of protection remain elusive. Tissue-resident memory T (TRM) cells have been implicated in protective immune responses against viral infections, but the role of TRM cells following mycobacterial infection is unknown. Using a mouse model of TB, we compared protection and lung cellular infiltrates of parenteral and mucosal BCG vaccination. Adoptive transfer and gene expression analyses of lung airway cells were performed to determine the protective capacities and phenotypes of different memory T cell subsets. In comparison to subcutaneous vaccination, intratracheal and intranasal BCG vaccination generated T effector memory and TRM cells in the lung, as defined by surface marker phenotype. Adoptive mucosal transfer of these airway-resident memory T cells into naive mice mediated protection against TB. Whereas airway-resident memory CD4+ T cells displayed a mixture of effector and regulatory phenotype, airway-resident memory CD8+ T cells displayed prototypical TRM features. Our data demonstrate a key role for mucosal vaccination-induced airway-resident T cells in the host defense against pulmonary TB. These results have direct implications for the design of refined vaccination strategies. BCG remains the only licensed vaccine against TB. Parenterally administered BCG has variable efficacy against pulmonary TB, and thus, improved prevention strategies and a more refined understanding of correlates of vaccine protection are required. Induction of memory T cells has been shown to be essential for protective TB vaccines. Mimicking the natural infection route by mucosal vaccination has been known to generate superior protection against TB in animal models; however, the mechanisms of protection have remained elusive. Here we performed an in-depth analysis to dissect the immunological mechanisms associated with superior mucosal protection in the mouse model of TB. We found that mucosal, and not subcutaneous, BCG vaccination generates lung-resident memory T cell populations that confer protection against pulmonary TB. We establish a comprehensive phenotypic characterization of these populations, providing a framework for future vaccine development.

Dataset Information

Targeting chronic COVID-19 lung injury; Tofacitinib can be used against tissue-resident memory T cells.

Publications

Targeting chronic COVID-19 lung injury; Tofacitinib can be used against tissue-resident memory T cells.

Similar Datasets

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