2. Academic Validation
  3. The C-C Chemokines CCL17 and CCL22 and Their Receptor CCR4 in CNS Autoimmunity

The C-C Chemokines CCL17 and CCL22 and Their Receptor CCR4 in CNS Autoimmunity

  • Int J Mol Sci. 2017 Nov 2;18(11):2306. doi: 10.3390/ijms18112306.
Stefanie Scheu 1,  Shafaqat Ali 2,  Christina Ruland 3 4,  Volker Arolt 5,  Judith Alferink 6 7 8
Affiliations

Affiliations

  • 1 Institute of Medical Microbiology and Hospital Hygiene, University of Düsseldorf, 40225 Düsseldorf, Germany. Stefanie.Scheu@uni-duesseldorf.de.
  • 2 Institute of Medical Microbiology and Hospital Hygiene, University of Düsseldorf, 40225 Düsseldorf, Germany. Shafaqat.Ali@med.uni-duesseldorf.de.
  • 3 Department of Psychiatry, University of Münster, 48149 Münster, Germany. Christina.Ruland@ukmuenster.de.
  • 4 Cells in Motion, Cluster of Excellence, University of Münster, 48149 Münster, Germany. Christina.Ruland@ukmuenster.de.
  • 5 Department of Psychiatry, University of Münster, 48149 Münster, Germany. Volker.Arolt@ukmuenster.de.
  • 6 Department of Psychiatry, University of Münster, 48149 Münster, Germany. judith.alferink@ukmuenster.de.
  • 7 Cells in Motion, Cluster of Excellence, University of Münster, 48149 Münster, Germany. judith.alferink@ukmuenster.de.
  • 8 Department of Psychiatry, Alexian Brothers Hospital, 48149 Münster, Germany. judith.alferink@ukmuenster.de.
PMID: 29099057 DOI: 10.3390/ijms18112306
Abstract

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). It affects more than two million people worldwide, mainly young adults, and may lead to progressive neurological disability. Chemokines and their receptors have been shown to play critical roles in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a murine disease model induced by active immunization with myelin proteins or transfer of encephalitogenic CD4⁺ T cells that recapitulates clinical and neuropathological features of MS. Chemokine ligand-receptor interactions orchestrate leukocyte trafficking and influence multiple pathophysiological cellular processes, including antigen presentation and cytokine production by dendritic cells (DCs). The C-C class chemokines 17 (CCL17) and 22 (CCL22) and their C-C Chemokine Receptor 4 (CCR4) have been shown to play an important role in homeostasis and inflammatory responses. Here, we provide an overview of the involvement of CCR4 and its ligands in CNS autoimmunity. We review key clinical studies of MS together with experimental studies in Animals that have demonstrated functional roles of CCR4, CCL17, and CCL22 in EAE pathogenesis. Finally, we discuss the therapeutic potential of newly developed CCR4 antagonists and a humanized anti-CCR4 antibody for treatment of MS.

Keywords

CCL17; CCL22; CCR4; CNS autoimmunity; chemokines; dendritic cells; experimental autoimmune encephalomyelitis; migration; multiple sclerosis; neuroinflammation.

Figures
Products