The murine CCR3 receptor regulates both eosinophilia and hyperresponsiveness in IgE-mediated allergic conjunctivitis

Background/aims: Allergic conjunctivitis is characterised by early-phase clinical symptoms and late-phase inflammation in the conjunctiva. The role of different chemokine receptors in allergic conjunctivitis, especially during the early-phase reaction, is still unclear. We investigated the importance of CC chemokine receptor (CCR) 3 in a murine model of IgE-mediated allergic conjunctivitis using CCR3-deficient (CCR3 ^-/-) mice. Methods: Allergic conjunctivitis was initiated in wild-type (WT) and CCR3 ^-/- mice by passive transfer of ragweed (RW)-specific IgE, followed by topical challenge with RW in eye drops. Early-phase reactions including clinical symptoms and vascular leakage, as well as late-phase eosinophil infiltration of the conjunctiva were evaluated. The expression of mRNAs in the conjunctiva was quantified by real-time PCR analysis. Results: The number of infiltrated eosinophils in the conjunctiva following RW challenge, was significantly higher in RW-IgE-sensitised WT mice compared with those sensitised with phosphate-buffered saline for WT, but this was not observed in similarly treated CCR3 ^-/- mice. The early-phase clinical symptoms and vascular leakage were also suppressed in CCR3 ^-/- mice. The number of conjunctival mast cells were not different between CCR3 ^-/- mice and WT mice, and the mRNAs for FcεRIα and the connective tissue-type mast cell proteases were detected in the conjunctiva of both WT and CCR3 ^-/- mice. RW-IgE-sensitised CCR3 ^-/- mice displayed significantly reduced expression of CCL2, CCL3, and IL-6 compared with WT mice. Conclusions: These results demonstrate a direct contribution of CCR3 to both the early-phase reaction and late-phase inflammation during ocular allergy.