CCR2: Affecting Autoimmunity via MCP1 interactions

Wed, 12/18/2013 - 14:00

CCR2, also known as CD192 (cluster of differentiation 192), is a chemokine receptor and is expressed by monocytes, activated T cells, B cells and natural killer cells. This protein is encoded by CCR2 gene in humans. CCR2 gene encodes two protein isoforms of a receptor for chemokines monocyte chemoattractant protein-1 (MCP1), MCP3 and MCP4. These chemokines bind and signal through CCR2 and mediate monocyte chemotaxis.

Chemokine receptors such as CCR2 are considered to play a key role in the pathogenesis in autoimmune diseases, including multiple sclerosis, rheumatoid arthritis and atherosclerosis (1). Most autoimmune diseases are marked by the infiltration of immune cells leading to inflammation and tissue damage. Many studies have addressed the molecule basis of monocyte recruitment in different autoimmune diseases and the conclusions pointed to a major role played by CCR2 and MCP-1. These findings suggest that by interfering CCR2-MCP-1 interaction may inhibit the progression of CCR2-dependent diseases.  Numerous pharmaceutical companies have report programs to identify CCR2 antagonists, and some clinical trials using CCR2 receptor blockers are already in progress, such as MLN-1202 for the treatment of rheumatoid arthritis (2).

CCR2 is shown to associate HIV progression: CCR2 acts as a co-receptor with CD4+ T cell for HIV-1 infection, and a conservative substitution (V64I) in the coding region of CCR2 has a significant impact on HIV progression but not on HIV-1 transmission (3). The CCR2V64I polymorphism of CCR2, in which an amino acid valine at position 64 is replaced by an isoleucine, is associated with a delay of 2-4 years in the progression of AIDS (4). CCR2 antagonist TBR-652, a dual blocker for both CCR2 and CCR5, shows potential activity against HIV (5).

Furthermore, recent work in mice shows that CCR2 plays an important role in Alzheimer’s progression: CCR2 is involved in removing beta-amyloid, the main Alzheimer’s-causing substance in the brain, and similar mechanism may apply in humans (6). CCR2 deficient mice (Tg2576) have been demonstrated to develop an accelerated Alzheimer’s-like pathology and a markedly impairs in microglial accumulation was observed (6). In addition, it was showed that augmenting CCR2-mediated beta-amyloid removal in CCR2 deficient mice results in improved memory and functioning. Similar approach may be applied in humans susceptible to Alzheimer’s (7).

Immunocytochemistry/Immunofluorescence: CCR2 Antibody Immunocytochemistry/Immunofluorescence: CCR2 Antibody

Novus Biologicals provides a wide range of CCR2 research reagents, including antibodies (for Western blotting, ELISA and Immunochemistry), lysates, recombinant proteins and peptides, and RNAi. Please contact us for further information.

  1. PMID: 11677088
  2. PMID: 18694362
  3. PMID: 9500612
  4. PMID: 9252328
  5. PMID: 21317794
  6. PMID: 17351623
  7. PMID: 22607625

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