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

  • Mol Immunol. 2026 Jul:195:93-100. doi: 10.1016/j.molimm.2026.05.001.
Jingheng Du  1 Jiaxin Wu  2 Xiukui Tan  1 Jingbin Xie  2 Zhudan Zhuang  3 Huifei Lan  3 Yunxia Xue  3 Ting Fu  3 Jingyi Gu  4 Zhijie Li  5 Jun Liu  6
Affiliations
  • 1. International Ocular Surface Research Center, Institute of Ophthalmology, and Key Laboratory for Regenerative Medicine, Jinan University, Guangzhou, China; Medical Experiment Research Center, School of Basic Medicine and Public Health, Jinan University, China; The Undergraduate Medical Innovation Capability Expansion Experimental Teaching Demonstration Center of Jinan University, China.
  • 2. International Ocular Surface Research Center, Institute of Ophthalmology, and Key Laboratory for Regenerative Medicine, Jinan University, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
  • 3. International Ocular Surface Research Center, Institute of Ophthalmology, and Key Laboratory for Regenerative Medicine, Jinan University, Guangzhou, China.
  • 4. Medical Experiment Research Center, School of Basic Medicine and Public Health, Jinan University, China; The Undergraduate Medical Innovation Capability Expansion Experimental Teaching Demonstration Center of Jinan University, China; Jinan-Puhua Joint Laboratory, Nansha, Guangzhou, China. Electronic address: [email protected].
  • 5. International Ocular Surface Research Center, Institute of Ophthalmology, and Key Laboratory for Regenerative Medicine, Jinan University, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China. Electronic address: [email protected].
  • 6. International Ocular Surface Research Center, Institute of Ophthalmology, and Key Laboratory for Regenerative Medicine, Jinan University, Guangzhou, China; The Undergraduate Medical Innovation Capability Expansion Experimental Teaching Demonstration Center of Jinan University, China; Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China. Electronic address: [email protected].
Abstract

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.

Keywords
Allergic conjunctivitis; CCL11; CSF1R; Eosinophil; Macrophage polarization.
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