CKLF1-C19 Attenuates Skin Inflammation in a Murine Model of Th2-Type Allergic Dermatitis

Abstract

Background: C19 is a C-terminal peptide derived from the Human chemokine-like factor (CKLF)1. It possesses the ability to trigger CC chemokine receptor (CCR)4 internalization and exhibits anti-inflammatory properties. We aim to investigate whether C19 can exert an inhibitory effect on the progression of inflammation in a murine model of T helper (Th)2-type allergic dermatitis, which is employed in studying human atopic dermatitis (AD). Methods: Type-2 T helper cell (Th2)-type allergic dermatitis was challenged on the back of female BALB/c mice with 2,4-dinitrofluorobenzene (DNFB) for 5 weeks. The experimental groups were treated with an intraperitoneal injection of double distilled water (ddH₂O), C19 (1 μg, 10 μg, and 100 μg), and hydrocortisone throughout the model establishment. Skin inflammation was scored, and serum and skin samples were collected after the experiment. Mast cells in the lesions were analyzed by toluidine blue staining. Expressions of serum immunoglobulin (Ig)E, skin interleukin (IL)-4, IL-17A, IL-25, and tumor necrosis factor (TNF)-α were determined and analyzed by Enzyme-Linked Immunosorbent Assay (ELISA). Results: The inflammation induced by DNFB in the mouse model was evident. C19 inhibited skin inflammation, skin thickening, and infiltration of mast cells into the dermis in BALB/c mice. The expressions of serum IgE, skin IL-4, IL-17A, IL-25, and TNF-α were reduced by intraperitoneal administration of C19 in high concentrations (10 μg and 100 μg). The expressions of serum IgE and skin IL-4 could also be reduced by a low concentration of C19 (1 μg). Conclusions: C19 mitigated skin inflammation and decreased the expressions of serum IgE, skin IL-4, IL-17A, IL-25, and TNF-α in a murine model of Th2-type allergic dermatitis. These findings propose that C19 could effectively treat human atopic dermatitis.