Pollen shells and soluble factors play non-redundant roles in the development of allergic conjunctivitis in mice

Purpose: We aimed to clarify the role of particulate allergen exposure to the conjunctiva in the development of allergic conjunctivitis. Methods: We administered ragweed pollen suspension, pollen extract, pollen shell, particulate air pollutants, and their combinations to the mouse conjunctiva five days a week without prior sensitization. Clinical signs were scored. Histological changes, cellular infiltrations, mRNA expressions, lymph node cell recall responses, and serum immunoglobulin levels were assessed. Immune cell-depleting antibodies and ST2 knockout mice were used to investigate the cellular and molecular requirements. Results: Pollen suspension, but not the extract or shell alone, induced robust eosinophilic conjunctivitis, accompanied by a proliferative response of epithelial cells. A combination of pollen extract and shell completely restored eosinophil accumulation. In addition, eosinophilic conjunctivitis was induced by a mixture of particulate air pollutants and pollen extract. Mechanistically, eosinophil accumulation was ameliorated by deficiency of the IL-33 receptor ST2 and abolished by depleting CD4(+) T cells. Pollen shells, but not the extract, induced IL-33 release from conjunctival epithelial cells in vivo. Conclusions: Our results indicate the non-redundant roles for the allergens' particulate properties and soluble factors in the development of allergic conjunctivitis.