Downregulation of Mirlet7 miRNA family promotes Tc17 differentiation and emphysema via de-repression of RORγt
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View abstract on PubMed
Summary
This summary is machine-generated.The let-7 microRNA (miRNA) family, reduced in emphysema, normally brakes T cell inflammation. Its loss promotes emphysema by increasing IL-17-producing T cells via RORγt.
Area Of Science
- Immunology
- Molecular Biology
- Pulmonology
Background
- Environmental air irritants like nanosized carbon black (nCB) drive inflammation, contributing to chronic obstructive pulmonary disease (COPD) and emphysema.
- The let-7 microRNA (miRNA) family is linked to IL-17-driven T cell inflammation, a key feature of lung inflammation.
- Reduced let-7 miRNA levels are observed in COPD patients, but its functional role in emphysema remains unclear.
Purpose Of The Study
- To investigate the functional consequence of let-7 miRNA downregulation on emphysema pathology.
- To elucidate the role of the let-7 miRNA family in T cell-mediated inflammation and emphysema development.
Main Methods
- Quantified let-7 miRNA cluster expression in lungs and T cells from human smokers with emphysema and in mouse models of emphysema.
- Utilized genetic ablation of let-7b/let-7c2 clusters in T cells and overexpression of let-7g in T cells in mouse models.
- Analyzed the impact on T cell populations, including CD8+IL17a+ T cells (Tc17) and CD4+IL17a+ T cells (Th17), and identified RORγt as a direct let-7 target.
Main Results
- let-7b/let-7c2 and let-7a1/let-7f1/let-7d miRNA clusters were reduced in emphysema lungs and T cells.
- Loss of the let-7b/let-7c2 cluster in T cells exacerbated cigarette smoke (CS)- or nCB-induced emphysema and enhanced Tc17 formation.
- Overexpression of let-7g in T cells conferred resistance to Tc17 and Th17 development upon nCB exposure, mediated by direct targeting of RORγt.
Conclusions
- The let-7 miRNA family acts as a molecular brake on Tc17 cell generation, crucial for mitigating emphysema.
- Downregulation of let-7 miRNA in T cells promotes emphysema by facilitating IL-17-mediated inflammation through RORγt.
- The let-7/RORγt axis represents a potential therapeutic target for managing IL-17-driven responses in emphysema.
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