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• W4377010989 abstract "Physiologically aged lungs are prone to senescence-associated pulmonary diseases (SAPD). This study aimed to determine the mechanism and subtype of aged T cells affecting alveolar type II epithelial (AT2) cells, which promote the pathogenesis of senescence-associated pulmonary fibrosis (SAPF). Cell proportions, the relationship between SAPD and T cells, and the aging- and senescence-associated secretory phenotype (SASP) of T cells between young and aged mice were analyzed using lung single-cell transcriptomics. SAPD was monitored by markers of AT2 cells and found to be induced by T cells. Furthermore, IFNγ signaling pathways were activated and cell senescence, SASP, and T cell activation were shown in aged lungs. Physiological aging led to pulmonary dysfunction and TGF-β1/IL-11/MEK/ERK (TIME) signaling-mediated SAPF, which was induced by senescence and SASP of aged T cells. Especially, IFNγ was produced by the accumulated CD4+ effector memory T (TEM) cells in the aged lung. This study also found that physiological aging increased pulmonary CD4+ TEM cells, IFNγ was produced mainly by CD4+ TEM cells, and pulmonary cells had increased responsiveness to IFNγ signaling. Specific regulon activity was increased in T cell subclusters. IFNγ transcriptionally regulated by IRF1 in CD4+ TEM cells promoted the epithelial-to-mesenchymal transition by activating TIME signaling and cell senescence of AT2 cells with aging. Accumulated IRF1+CD4+ TEM produced IFNγ in lung with aging and anti-IRF1 primary antibody treatment inhibited the expression of IFNγ. Aging might drive T cell differentiation toward helper T cells with developmental trajectories and enhance cell interactions of pulmonary T cells with other surrounding cells. Thus, IFNγ transcribed by IRF1 in CD4+ effector memory T cells promotes SAPF. IFNγ produced by CD4+ TEM cells in physiologically aged lungs could be a therapeutic target for preventing SAPF." @default.
• W4377010989 created "2023-05-19" @default.
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• W4377010989 date "2023-01-01" @default.
• W4377010989 modified "2023-09-30" @default.
• W4377010989 title "IFNγ Transcribed by IRF1 in CD4⁺ Effector Memory T Cells Promotes Senescence-Associated Pulmonary Fibrosis" @default.
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• W4377010989 doi "https://doi.org/10.14336/ad.2023.0320" @default.
• W4377010989 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37199578" @default.
• W4377010989 hasPublicationYear "2023" @default.
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