Reply to Othy et al.: Dendritic cell-specific expression of CCR4 is required for development of EAE

Alferink, Judith; Poppensieker, Karola; Otte, David-Marian; Klotz, Luisa; Scheu, Stefanie; Maier, Wolfgang; Zimmer, Andreas

doi:10.1073/pnas.1209505109

Cited by 3 publications

(1 citation statement)

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“…Th1 and Th2 clones (or polarized Th cell subsets) may express different chemokine receptor profiles associated with specific migratory capacities, with Th1 clones preferentially expressing CXCR3 and CCR5, and Th2 cells expressing higher levels of CCR4 and CCR8 [ 29 , 30 ]. Of note, also human and mouse Th17 cells, highly relevant in CNS autoimmune pathology, have been described to express CCR4 [ 31 , 32 , 33 ]. Specifically, human memory Th17 cells were found to coexpress CCR4 together with CCR6.…”

Section: C-c Chemokine Receptor 4 (Ccr4) and Its Ligands C-c Chemomentioning

confidence: 99%

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

Scheu

Ali

Ruland

et al. 2017

IJMS

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115

105

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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.

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