The impact of the immune system on lung injury and regeneration in chronic obstructive pulmonary disease.

Abstract

Chronic obstructive pulmonary disease (COPD) is a devastating respiratory condition that manifests via persistent inflammation, emphysema development and small airway remodeling. Lung regeneration is defined as the ability of the lung to repair itself after injury by the proliferation and differentiation of progenitor cell populations and becomes impaired in the COPD lung as a consequence of cell intrinsic epithelial stem cell defects and signals from the microenvironment. Although the loss of structural integrity and lung regenerative capacity are critical for disease progression, our understanding of the cellular players and molecular pathways that hamper regeneration in COPD remains limited. Intriguingly, despite being a key driver of COPD pathogenesis, the role of the immune system in regulating lung regenerative mechanisms is understudied. In this review, we summarize recent evidence on the contribution of immune cells to lung injury and regeneration. We focus on four main axes; the mechanisms via which myeloid cells cause alveolar degradation, the consequences of inefficient apoptotic cell removal, the formation of tertiary lymphoid structures and the production of autoreactive antibodies and the effects of innate and adaptive immune cell signaling on alveolar epithelial proliferation and differentiation. We finally provide insight on how recent technological advances in omics technologies and human ex vivo lung models can delineate immune cell-epithelium crosstalk and expedite precision pro-regenerative approaches toward reprogramming the alveolar immune niche to treat COPD.