Role of TARC/CCL17 and CTACK/CCL27 in the Pathogenesis of Atopic Dermatitis

TARC/CCL17 is designated as a Th2 type chemokine since it binds to CCR4. CTACK/CCL27 is a ligand for CCR10 and is selectively expressed in skin. Atopic dermatitis (AD) is a chronic inflammatory skin disease that is characterized by the predominant infiltration of Th2-type cells, especially in the acute phase. We have determined that serum levels of TARC and CTACK are elevated in AD patients and reflect the disease activity of AD. We investigated the regulation of production of TARC and CTACK from the human keratinocyte (KC) cell line, HaCaT cells. Production of both was upregulated after stimulation with inflammatory cytokines TNF-α/IFN-γ and TNF-α/IL-1β, respectively, and the upregulated production was downregulated by adding inhibitors for nuclear factor kappa B (NFκB) and p38. We have created transgenic (Tg) mice in which TARC or CTACK is overexpressed in KC. Interestingly, both TARC Tg mice and CTACK Tg mice show enhanced contact hypersensitivity to Th2, but not to Th1 stimuli. AD-like conditions such as increased number of mast cells and elevated levels of serum IgE were observed in both Tg mice by Th2-type stimuli. Thus, TARC and CTACK may participate in the pathogenesis of Th2-shifted skin diseases such as AD. Keywords: Chemokine, TARC/CCL17, CTACK/CCL27, atopic dermatitis, keratinocytes, transgenic mice