Abstract
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.
Keywords:
Chemokine receptor; Experimental autoimmune encephalomyelitis.
Copyright © 2015 Elsevier B.V. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Cell Proliferation / drug effects
-
Cell Proliferation / genetics
-
Cytokines / metabolism
-
Dose-Response Relationship, Drug
-
Encephalomyelitis, Autoimmune, Experimental / chemically induced
-
Encephalomyelitis, Autoimmune, Experimental / drug therapy*
-
Encephalomyelitis, Autoimmune, Experimental / genetics
-
Female
-
Fluoresceins / therapeutic use*
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Myelin-Oligodendrocyte Glycoprotein / immunology
-
Myelin-Oligodendrocyte Glycoprotein / toxicity
-
Peptide Fragments / immunology
-
Peptide Fragments / toxicity
-
Receptors, CCR4 / antagonists & inhibitors*
-
Receptors, CCR4 / deficiency
-
Receptors, CCR4 / genetics
-
T-Lymphocytes / drug effects
-
T-Lymphocytes / metabolism
-
Time Factors
Substances
-
2-(3-hydroxy-4,5-diiodo-6H-6-oxoxanthen-9-yl)benzoic acid
-
Ccr4 protein, mouse
-
Cytokines
-
Fluoresceins
-
Myelin-Oligodendrocyte Glycoprotein
-
Peptide Fragments
-
Receptors, CCR4
-
myelin oligodendrocyte glycoprotein (35-55)