Insights on the role of the chemokine CCL8 in pathology

Chemokine (C-C motif) ligand 8 (CCL8), also known as monocyte chemotactic protein-2 (MCP-2) is involved in immune cell recruitment, inflammation, and disease progression. While essential for host defense, dysregulated CCL8 expression and signaling contribute to the progression of infectious diseases, inflammatory disorders, and various cancers. CCL8 is also transcriptionally regulated under hypoxic conditions, linking it to the remodeling of the tumor microenvironment, placental dysfunction, and ischemic injury. In infections such as HIV, tuberculosis, and viral pneumonias, CCL8 regulates immune cell trafficking, enhancing both pathogen clearance and excessive immune activation. Inflammatory conditions such as graft-versus-host disease (GVHD), idiopathic pulmonary fibrosis (IPF), and preeclampsia are also associated with elevated CCL8 expression, promoting immune dysregulation and tissue damage. In allergic diseases such as asthma and atopic dermatitis, CCL8 contributes to Th2-driven inflammation by recruiting eosinophils and CCR8⁺ T cells to affected tissues. In cancer, CCL8 promotes tumor progression, metastasis, immune evasion, and therapeutic resistance through the recruitment of immunosuppressive cells such as M2 macrophages and regulatory T cells. Given its widespread role in immune modulation, CCL8 represents both a potential diagnostic biomarker and a therapeutic target. Recent advances in antibody-based therapies and ligand-directed strategies, including cytotoxic CCL8 analogs, highlight new opportunities for translational application. Further research is needed to clarify its specific mechanisms and explore targeted interventions that modulate CCL8 signaling for clinical applications.