Chemokine receptor gene expression in giant papillae of atopic keratoconjunctivitis.

PURPOSE Major chemokine receptors in the giant papillae of atopic keratoconjunctivitis (AKC) have yet to be determined. We evaluated chemokine receptor genes and their ligand expressions in upper tarsal conjunctival giant papillae of AKC with atopic dermatitis and/or asthma. METHODS CC, CXC, and CX3C chemokine receptor (R) gene expression levels in giant papillae of five clinically active AKC patients and in three age matched non-allergic control conjunctiva were measured with a multi-probe ribonuclease protection assay (RPA) system. The ligands of abundant chemokine receptors in the giant papillae were examined by immunohistochemistry or reverse transcription-polymerase chain reaction. Interleukin (IL)-4 and IL-13 gene expression levels were measured with RPA. Ligand expression in cultured human conjunctival fibroblasts was examined by reverse transcription-polymerase chain reaction. RESULTS High CXCR4 and CCR4 gene expression levels were detected in the giant papillae of all (CXCR4) and four out of five (CCR4) patients. As a CCR4-ligand, thymus and activation regulated cytokine (TARC/CCL17) rather than macrophage derived chemokine (MDC/CCL22), was predominant immunohistochemicaly in the giant papillae. Giant papillae with high CCR4 gene expression levels showed high IL-4 and IL-13 expression. Cultured human conjunctival fibroblasts express stromal cell derived factor-1 (SDF-1/CXCL12) in vitro. CONCLUSIONS CXCR4 and CCR4 are the major chemokine receptor genes expressed in the giant papillae of AKC with atopic dermatitis and/or asthma. Our findings suggest a role for CXCR4 and CCR4 in the formation of giant papillae.