Lung Dendritic Cells: Shaping Immune Responses throughout Chronic Obstructive Pulmonary Disease Progression

Hallmarks of chronic obstructive pulmonary disease (COPD) include innate inflammation and remodeling of small airways, which begin in early disease, and the development of lung lymphoid follicles (LLF), indicative of adaptive immunity, in more spirometrically severe stages. Common to these processes in all stages is orchestration by dendritic cells (DCs). Recently improved understanding of the analogous lung DC subsets in humans and mice has allowed for better integration and interpretation of the experimental and clinical pathological literature. In this review, we summarize the evidence from human and animal studies to place lung DCs into the context of COPD pathogenesis. We highlight recent studies that demonstrate a potential role for DCs in airway remodeling and that call into question the long-standing belief that intraepithelial DCs actively sample airway lumens. We discuss how DCs drive LLF formation directly and indirectly and also examine the ability of DCs within LLF to instruct downstream effector functions of natural killer cells, CD4⁺ T cells, and regulatory T cells. Greater awareness of the multifaceted functions of DCs will be essential in the quest to identify new therapeutic modalities to treat COPD.