The following is a summary of “PPARγ attenuates cellular senescence of alveolar macrophages in asthma-COPD overlap,” published in the April 2024 issue of Pulmonology by Wan et al.
Asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) represents a multifaceted clinical entity characterized by the convergence of key features from both asthma and COPD, particularly prevalent in older individuals. Despite its clinical significance, the underlying pathophysiology of ACO remains largely unexplored. In this study, the researchers endeavored to unravel the intricate landscape of inflammatory cells within ACO, scrutinize the phenomenon of cellular senescence within these cells, and elucidate the genetic determinants governing senescence regulation.
Employing an integrative approach, investigators conducted comprehensive bioinformatic analyses leveraging a publicly available single-cell RNA sequencing (scRNA-Seq) dataset derived from the lung tissues of patients with ACO. The investigations unveiled monocytes/macrophages as the predominant cell type within ACO lung tissues, constituting over 50% of the analyzed cell population. Intriguingly, these lung monocytes/macrophages exhibited a reduced prevalence of senescence, as evidenced by lower enrichment scores of SenMayo and diminished expression levels of cellular senescence markers.
Similarly, analyses of an independent cohort study, Immune Mechanisms Severe Asthma (IMSA), corroborated these findings, demonstrating a comparable reduction in senescence prevalence among patients with severe asthma, particularly in airway CD206 + macrophages, concomitant with heightened cytokine expression (e.g., IL-4, IL-13, and IL-22). Further dissection of cellular subtypes identified alveolar macrophages as a key driver of senescence within ACO. Differential gene expression analyses highlighted genes associated with oxidation-reduction, cytokine signaling, and growth factors as pivotal regulators of senescence in alveolar macrophages, with Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) emerging as a prominent regulatory node modulating the senescent signature.
In summary, the findings underscore the pivotal role of macrophage senescence, particularly alveolar macrophages, in the pathophysiology of ACO. Furthermore, identifying PPARγ as a potential therapeutic target holds promise for interventions aimed at mitigating senescence-associated processes in ACO, thereby offering novel avenues for therapeutic intervention in this complex clinical entity.
Source: respiratory-research.biomedcentral.com/articles/10.1186/s12931-024-02790-6