How Do Innate Immune Cells Contribute to Airway Remodeling in COPD Progression?

Figures & data

Table 1 Major Cell Types in the Innate Immune System That Contribute to Airway Remodeling in COPD

	Cellular Activity	Major Cytokines	Function
Epithelial cell	Goblet cell production Mucus hypersecretion Epithelial cell depolarization EMT	NF-κB↓ IL-8↑ EGFR↑	Mucus hypersecretion Non-specific airway inflammation Epithelial phenotypic alteration
Dendritic cell	Exposed to antigen Recruited and migrate toward draining lymph nodes Activate T and B cells Impaired maturation → bacterial colonization↑
Macrophage	Aberrant functional phenotype Immune tolerance↑ Decreasing phagocytic capacity	IL-8↑ TNF-α↑ MMPs↑	Pro-inflammatory potential↑ Anti-inflammatory potential↓ ECM deposition Elastin breakdown
Neutrophil	Recruited by DAMPs	ROS↑ MMPs↑	Neutrophilic airway inflammation Disturbed protease-antiprotease balance
NKT cell	Slightly ↑ or ↓ Dampened cytotoxicity potential in long-term disease	Granzyme B↑ Perforin↑ CD94↓ IFN-γ↑ TNF-α↑	Epithelial and parenchymal destruction Anti-inflammatory mediators↓ Enhance the function of DCs, T cells, and B cells

Notes: ↑, increased during COPD progression; ↓, decreased during COPD progression; (-) no change during COPD progression.

Abbreviations: NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; IL-8, interleukin-8; EGFR, epidermal growth factor receptor; EMT, epithelial-mesenchymal transition; TNF-α, tumor necrosis factor alpha; MMPs, matrix metalloproteinases; ECM, extracellular matrix; DAMPs, damage-associated molecular patterns; ROS, reactive oxygen species; NKT cell, natural killer T cell; IFN-γ, interferon-gamma.

Table 2 Immune-Modulatory Approaches to Delay COPD Airway Remodeling

Immune-Modulatory Approach	Mechanism
Inhaled corticosteroid	ECM deposition↓
	EMT↓
	Inflammatory cell infiltration↓
Macrolide	Inflammatory cascade↓
	Adhesion molecule expression↓
	Neutrophil chemotaxis and activation↓
	Monocyte-macrophage differentiation↓
Fluoroquinolones	NF-κB activation↓
Ceftaroline	TLR expression↓
Vitamin D receptor	Retain phagocytic capacity
	NF-κB and p38 MAPK cascade↓→ MMPs and TGF-β ↓ → airway wall destruction↓ fibrotic repair↓
Antibodies of pro-inflammatory cytokines	IL-4, IL-5, IL-13, and IgE↓

Notes: ↑, increased during COPD progression; ↓, decreased during COPD progression; (-), no change during COPD progression.

Abbreviations: ECM, extracellular matrix; EMT, epithelial-mesenchymal transition; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; TLR, toll-like receptors; p38 MAPK, p38 mitogen-activated protein kinase; MMPs, matrix metalloproteinases; TGF-β, transforming growth factor beta; IL, interleukin; IgE, immunoglobulin E.