Table 2.
Key chemokine-receptor axes in elderly asthma: Mechanisms and therapeutic implications
| Chemokine | Primary receptor(s) | Main cellular sources | Principal target cell(s) | Receptor expression on target cells (verified) | Role in elderly asthma pathogenesis | Therapeutic implications |
|---|---|---|---|---|---|---|
| CCL11 (Eotaxin-1) | CCR3 | Airway epithelial cells, fibroblasts, endothelial cells [22] | Eosinophils | Yes (confirmed by flow cytometry and immunohistochemistry) [22] | Drives persistent eosinophilic inflammation; correlates with airway obstruction and exacerbation frequency | CCR3 antagonists (preclinical); may benefit elderly patients with persistent eosinophilia |
| CXCL8 (IL-8) | CXCR1, CXCR2 | Airway epithelial cells, macrophages, neutrophils [20] | Neutrophils | Yes (CXCR1/2 expression confirmed on human neutrophils) [20] | Mediates neutrophilic inflammation; linked to steroid resistance and airway senescence | CXCR2 antagonists (e.g., danirixin, AZD5069); candidate for neutrophilic elderly asthma |
| CCL2 (MCP-1) | CCR2 | Airway epithelial cells, smooth muscle cells, monocytes [21] | Monocytes, macrophages | Yes (CCR2 expression confirmed on CD14+ monocytes) [21] | Recruits inflammatory monocytes; amplifies and sustains chronic airway inflammation | CCR2 antagonists (e.g., PF-04136309); under investigation for chronic inflammatory diseases |
| CX3CL1 (Fractalkine) | CX3CR1 | Airway epithelial cells, endothelial cells, smooth muscle cells [26, 27] | Macrophages, T cells, smooth muscle cells | Yes (CX3CR1 expression confirmed on macrophages and T cells) [26, 27] | Dual role: promotes leukocyte adhesion during acute inflammation; facilitates resolution via CX3CR1+ macrophages; chronic dysregulation contributes to remodeling | CX3CR1 modulators (preclinical); context-dependent targeting required |
| CXCL12 (SDF-1) | CXCR4, CXCR7 | Fibroblasts, endothelial cells, bone marrow stromal cells [29, 30] | Pericytes, fibrocytes, stem cells | Yes (CXCR4 expression confirmed on pericytes and fibrocytes) [30] | Drives pericyte migration → airway smooth muscle thickening; also involved in tissue repair and stem cell homing | CXCR4 antagonists (e.g., AMD3100/plerixafor); stem cell-based therapies targeting SDF-1/CXCR4 axis |
Note: The column titled “Receptor Expression on Target Cells (Verified?)” indicates whether the target cells listed in the adjacent column have been shown to express the corresponding chemokine receptor in published studies (citations provided). Methods for verifying expression include flow cytometry, immunohistochemistry, and/or transcriptomic analysis, as reported in the cited literature. Abbreviations: CCL11: C-C motif chemokine ligand 11; CCR3: C-C chemokine receptor 3; CXCL8: C-X-C motif chemokine ligand 8; CXCR1: C-X-C chemokine receptor 1; CXCR2: C-X-C chemokine receptor 2; CCL2: C-C motif chemokine ligand 2; MCP-1: Monocyte chemoattractant protein 1; CCR2: C-C chemokine receptor 2; CX3CL1: C-X3-C motif chemokine ligand 1; CX3CR1: C-X3-C chemokine receptor 1; CXCL12: C-X-C motif chemokine ligand 12; SDF-1: Stromal cell-derived factor 1; CXCR4: C-X-C chemokine receptor 4; CXCR7: C-X-C chemokine receptor 7.