Chemokine receptor modulation via specialized pro-resolving mediator pathways

Specialized pro-resolving mediator pathways refer to the process by which a family of endogenous lipid mediators (SPMs)—including resolvins, protectins, maresins, and lipoxins—bind and activate a set of G protein-coupled receptors (such as FPR2/ALX, GPR32, GPR18, ChemR23) on immune and structural cells, leading to active termination of inflammation, enhanced host defense, promotion of phagocytosis, tissue repair, and restoration of immune homeostasis. This pathway is increasingly recognized as distinct from classical anti-inflammatory mechanisms, offering a focused approach for resolving chronic inflammatory diseases and infections with significant translational therapeutic potential. However, chemokine receptor modulation by SPMs is a field with ongoing debate, as not all proposed receptor-ligand pairings have been functionally validated in humans and development of synthetic SPM drugs is still in early research stages.

SPMs act as agonists at specific GPCRs (e.g., FPR2/ALX, GPR32, GPR18, ChemR23), leading to anti-inflammatory and pro-resolving responses. Limiting neutrophil influx, stimulating phagocytosis, and promoting clearance of cellular debris.