The chemokine receptor CCR3 participates in tissue remodeling during atopic skin inflammation

Recent studies provided insights into the recruitment and activation pathways of leukocytes in atopic dermatitis, however, the underlying mechanisms of tissue remodeling in atopic skin inflammation remain elusive.

To identify chemokine-mediated communication pathways regulating tissue remodeling during atopic skin inflammation.

Analysis of the chemokine receptor repertoire of human dermal fibroblasts using flow cytometry and immunofluorescence. Quantitative real-time polymerase chain reaction and immunohistochemical analyses of chemokine expression in atopic vs. non-atopic skin inflammation. Investigation of the function of chemokine receptor CCR3 on human dermal fibroblasts through determining intracellular Ca(2+) mobilization, cell proliferation, migration, and repair capacity.

Analyses on human dermal fibroblasts showed abundant expression of the chemokine receptor CCR3 in vitro and in vivo. Among its corresponding ligands (CCL5, CCL8, CCL11, CCL24 and CCL26) CCL26 demonstrated a significant and specific up-regulation in atopic when compared to psoriatic skin inflammation. In vivo, epidermal keratinocytes showed most abundant CCL26 protein expression in lesional atopic skin. In structural cells of the skin, TH2-cytokines such as IL-4 and IL-13 were dominant inducers of CCL26 expression. In dermal fibroblasts, CCL26 induced CCR3 signaling resulting in intracellular Ca(2+) mobilization, as well as enhanced fibroblast migration and repair capacity, but no proliferation.

Taken together, findings of the present study suggest that chemokine-driven communication pathways from the epidermis to the dermis may modulate tissue remodeling in atopic skin inflammation.