C-C chemokine receptor type 4 antagonist Compound 22 ameliorates experimental autoimmune encephalomyelitis

•CCR4 antagonist Compound 22 ameliorated the clinical symptoms of EAE.•Compound 22 inhibits Th1 and Th17 polarization.•Compound 22 downregulated the T cell priming.•CCR4 antagonism might be used to treat MS.

Chemokines and chemokine receptors play important roles in the immune response. We previously reported the pathogenic role of C-C chemokine receptor type 4 (CCR4) in experimental autoimmune encephalomyelitis (EAE). Here, we examined whether CCR4 antagonism modulates the disease course of EAE. Wild-type and CCR4-knockout mice were induced EAE and were administered Compound 22, an antagonist of CCR4. Compound 22 significantly ameliorated the severity of EAE in wild-type mice, but not in the CCR4-knockout mice. Compound 22 inhibited Th1 and Th17 polarization of antigen-induced T-cell responses. Therefore, CCR4 antagonists might be potential therapeutic agents for multiple sclerosis.

Graphical abstractCCR4 antagonist, Compound 22 significantly ameliorated the severity of EAE in wild-type mice, but not in the CCR4-knockout mice. CCR4 antagonism might be potential therapeutic agents for multiple sclerosis.Download high-res image (74KB)Download full-size image