CSF1R signaling contributes to macrophage-associated CCL11 production and eosinophil recruitment in murine allergic conjunctivitis.

Allergic conjunctivitis (AC) is a prevalent ocular surface inflammatory disorder with limited therapeutic options. In this study, we investigated the role of colony-stimulating factor 1 receptor (CSF1R) in an ovalbumin (OVA)-induced murine model of AC. Conjunctival expression of CSF1R and its ligands, interleukin-34 (IL-34) and colony-stimulating factor 1 (CSF1), was significantly upregulated following OVA challenge. Pharmacological inhibition of CSF1R with BLZ945 alleviated clinical symptoms, reduced the infiltration of CD45⁺ leukocytes and eosinophils, and attenuated an M2-associated macrophage phenotype in the conjunctiva. Similar suppression of eosinophil infiltration was observed with a second CSF1R inhibitor, AZD7507. In addition, conjunctival CD206⁺ macrophages with an M2-associated phenotype expressed C-C motif chemokine ligand 11 (CCL11), which was elevated in AC and downregulated by CSF1R inhibition. Recombinant CCL11 significantly restored eosinophil infiltration in BLZ945-treated mice, supporting a role for CCL11 as a downstream effector of CSF1R signaling in this model. Collectively, these findings support a contributory role for CSF1R signaling in macrophage-associated eosinophilic inflammation in murine AC and suggest that targeting CSF1R may represent a potential therapeutic strategy for ocular allergic disease.