Roles of Myeloid and Lymphoid Cells in the Pathogenesis of Chronic Obstructive Pulmonary Disease

Abstract

Chronic obstructive pulmonary disease (COPD) is currently the third largest cause of human mortality in the world after stroke and heart disease. COPD is characterized by sustained inflammation of the airways, leading to destruction of lung tissue and declining pulmonary function. The main risk factor is known to be cigarette smoke currently. However, the strategies for prevention and treatment have not altered significantly for many years. A growing body of evidences indicates that the immune system plays a pivotal role in the pathogenesis of COPD. The repeated and progressive activation of immune cells is at least in part the source of this chronic inflammation. In this review paper, we have conducted an extensive literature search of the studies of immune cells in COPD patients. The objective is to assess the contributions of different immune cell types, the imbalance of pro/anti-inflammatory immune cells, such as M1/M2 macrophages, Tc1/Tc10, and Th17/Treg, and their mediators in the peripheral blood as well as in the lung to the pathogenesis of COPD. Therefore, understanding their roles in COPD development will help us find the potential target to modify this disease. This review focuses predominantly on data derived from human studies but will refer to animal studies where they help understand the disease in humans.

Keywords: COPD pathogenesis; chronic obstructive pulmonary disease; immune cells; immune system; immune target.

Figure 1

Inflammatory cells involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). COPD monocytes leave the circulation, migrate into the lung, and differentiate into M2-like macrophages by sensing growth-related oncogene (GRO)/CXCL1 and neutrophil-activating peptide (NAP)-2/CXCL7 (❶). In lung, cigarette smoke extract (CSE) induces alveolar macrophages (AMs) to produce IL-8/CXCL8 (❷), which recruits circulating neutrophils (❸). Neutrophils produce neutrophil elastase to inhibit dendritic cell (DC) maturation (❹) and decline pulmonary function (❺). Moreover, AM-induced BAFF could promote B cell development and lymphoid follicle maintenance (❻), which recruit peripheral B cells via BLC/CXCL13 or SDF1/CXCR12. Activated B cells produce a large amount of antibodies (❻), leading to exacerbated COPD severity. AM-expressing D6 promotes granzyme B and perforin-expressing TC1 response, which exacerbate COPD severity (❼). In another aspect, COPD epithelial cells secret MIP-3α/CCL20, resulting in increased recruitment of dendritic cells and Th17 (❽). IL-17F further promotes lung epithelial cells to secret CCL20 (❾). Neutrophil-derived serine protease induces epithelial cells to secrete more mucin to exacerbate COPD severity (❿). The crosstalk between adaptive and innate immune cells contributes to the pathogenesis of COPD.