Expression of Chemokine Receptor CCR4 and Its Ligands (CCL17 and CCL22) in Murine Contact Hypersensitivity

Abstract

Chemokine receptor CCR4 and its ligands (CCL17 and CCL22) are important for the recruitment of memory T cells into the skin in various cutaneous immune diseases. However, information on CCR4 and its ligands in contact hypersensitivity is relatively limited. In this study, we investigated the expression of CCR4, CCL17, and CCL22 in a mouse model of contact hypersensitivity to oxazolone. Contact sensitization to oxazolone increased the proportions of memory CD4+ T cells in the draining lymph nodes, spleen, and peripheral blood. Although CCR4+ mRNA and CCR4+ cells were detectable in naive mouse lymph nodes, they significantly increased in the sensitized mice. The majority of CCR4+ cells in both control and sensitized mouse lymph nodes were CD4+ T cells. In the skin of naive mice, the mRNAs for CCR4, CCL17, and CCL22 were detectable, but only CCL17 and CCL22 proteins were constitutively expressed in the skin, particularly in the epidermis. Interestingly, the mRNAs for CCR4 and its two ligands were significantly elevated in the inflamed skin of mice with contact hypersensitivity to oxazolone. Furthermore, a subpopulation of cells that infiltrated the skin was CCR4+ cells. Finally, the expression of CCL17 and CCL22 proteins was significantly enhanced in the epidermis of inflamed skin. Thus, our study provides direct evidence for the presence of CCR4 and its ligands in mouse contact hypersensitivity.