Tissue-resident memory T (TRM) cells are a unique T cell population that exhibits long-term persistence in non-lymphoid tissues. To establish local residency, TRM progenitors gradually acquire distinct functional and migratory features such as: upregulation of molecules for tissue retention such as CD103 and CD69. Recent studies confirm that TRM cells are more efficient protecting tissue from recurrent infections as compared to memory T cells in circulation.
In a study published in Advanced Science, a research team led by Prof. LIU Xiaolong from the Center for Excellence in Molecular Cell Science (Shanghai Institute of Biochemistry and Cell Biology) of the Chinese Academy of Sciences reveals the distinct function of CD103+ T cells in lung tumorigenesis and identifies a potential immuno-dysregulation in the aged lung which contributes to tumorigenesis.
In this study, researchers show that the aged lung exhibits a specific decline of CD103+ T cells which belong to the tissue-resident T cell compartment. To study whether the decline of CD103+ T cells alters tissue fitness, using a mouse model with Med23 depletion in T cells (Med23-/-), they find a strong association between the decline of CD103+ T cells and spontaneous alveolar epithelial type II (AT2) cell-originated lung adenocarcinomas.
The major pro-tumorigenic event in the Med23-/- AT2 cells is mapped to the oxidative stress, and further functional experiments prove the CD103+ T cells eliminate AT2 cells bearing oxidative stress to preventROS-dependent tumorigenesis. Correspondingly, they find a significant correlation between the increased oxidative-stress-bearing AT2 cells and the decreased formation of lung CD103+ T cells in human lung samples.
Overall, this study establishes the vital function of CD103+ T cells in surveilling oxidative-stressed epithelial cells to prevent malignancies, and underscores specific decline in CD103+ T cells as a key feature in the aged lung. Importantly, this study provides novel insights into the regional immune regulations against malignancies arising from oxidative stress and highlights the decline of CD103+ T cells might represent a key feature of the aged T cell compartment contributing to the higher incidence of lung cancers in the aged population.
CD103+ T cells eliminate oxidative-stressed somatic cells to prevent lung tumorigenesis
Reference: https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202503557
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