Université de Reims Champagne Ardenne, Immuno-Régulation dans les Maladies Auto-Immunes, Inflammatoires et le Cancer (IRMAIC), Reims, France.
Institut Godinot, Unicancer, Reims, France.
Am J Physiol Lung Cell Mol Physiol. 2024 Jun 1;326(6):L812-L820. doi: 10.1152/ajplung.00306.2023. Epub 2024 May 7.
Chronic obstructive pulmonary disease (COPD) is a condition characterized by chronic airway inflammation and obstruction, primarily caused by tobacco smoking. Although the involvement of immune cells in COPD pathogenesis is well established, the contribution of innate lymphoid cells (ILCs) remains poorly understood. ILCs are a type of innate immune cells that participate in tissue remodeling processes, but their specific role in COPD has not been fully elucidated. During COPD, the breakdown of pulmonary elastin generates elastin peptides that elicit biological activities on immune cells. This study aimed to investigate the presence of ILC in patients with COPD and examine the impact of elastin peptides on their functionality. Our findings revealed an elevated proportion of ILC2 in the peripheral blood of patients with COPD, and a general activation of ILC as indicated by an increase in their cytokine secretion capacity. Notably, our study demonstrated that serum from patients with COPD promotes ILC2 phenotype, likely due to the elevated concentration of IL-5, a cytokine known to favor ILC2 activation. Furthermore, we uncovered that this increase in IL-5 secretion is partially attributed to its secretion by macrophages upon stimulation by elastin peptides, suggesting an indirect role of elastin peptides on ILC in COPD. These findings shed light on the involvement of ILC in COPD and provide insights into the potential interplay between elastin breakdown, immune cells, and disease progression. Further understanding of the mechanisms underlying ILC activation and their interaction with elastin peptides could contribute to the development of novel therapeutic strategies for COPD management. Elastin-derived peptides, generated following alveolar degradation during emphysema in patients with COPD, are able to influence the response of type 2 innate lymphoid cells. We show that the orientation of innate lymphoid cells in patients with COPD is shifted toward a type 2 profile and that elastin peptides are indirectly participating in that shift through their influence of macrophages, which in turn impact innate lymphoid cells.
慢性阻塞性肺疾病（COPD）是一种以慢性气道炎症和阻塞为特征的疾病，主要由吸烟引起。虽然免疫细胞在 COPD 发病机制中的作用已得到充分证实，但先天淋巴细胞（ILC）的作用仍知之甚少。ILC 是一种参与组织重塑过程的先天免疫细胞，但它们在 COPD 中的具体作用尚未完全阐明。在 COPD 中，肺弹力蛋白的破坏会产生弹力蛋白肽，这些肽会对免疫细胞产生生物学活性。本研究旨在探讨 COPD 患者中 ILC 的存在，并研究弹力蛋白肽对其功能的影响。我们的研究结果显示，COPD 患者外周血中 ILC2 的比例升高，ILC 的一般激活表现为细胞因子分泌能力增强。值得注意的是，我们的研究表明，COPD 患者的血清促进了 ILC2 表型的出现，这可能是由于细胞因子 IL-5 的浓度升高所致，而 IL-5 是一种促进 ILC2 激活的细胞因子。此外，我们发现这种 IL-5 分泌的增加部分归因于弹力蛋白肽刺激后巨噬细胞的分泌，提示弹力蛋白肽在 COPD 中对 ILC 具有间接作用。这些发现揭示了 ILC 在 COPD 中的作用，并为弹力蛋白分解、免疫细胞和疾病进展之间的潜在相互作用提供了新的认识。进一步了解 ILC 激活的机制及其与弹力蛋白肽的相互作用，可能有助于开发 COPD 管理的新治疗策略。COPD 患者肺气肿时肺泡降解产生的弹力蛋白衍生肽能够影响 2 型先天淋巴细胞的反应。我们发现 COPD 患者的先天淋巴细胞定向向 2 型表型转移，弹力蛋白肽通过其对巨噬细胞的影响间接参与该转移，而巨噬细胞又反过来影响先天淋巴细胞。
