An emerging role for eotaxins in neurodegenerative disease.
Eotaxins are C-C motif chemokines first identified as potent eosinophil chemoattractants. They facilitate eosinophil recruitment to sites of inflammation in response to parasitic infections as well as allergic and autoimmune diseases such as asthma, atopic dermatitis, and inflammatory bowel disease. The eotaxin family currently includes three members: eotaxin-1 (CCL11), eotaxin-2 (CCL24), and eotaxin-3 (CCL26). Despite having only ~30% sequence homology to one another, each was identified based on its ability to bind the chemokine receptor, CCR3. Beyond their role in innate immunity, recent studies have shown that CCL11 and related molecules may directly contribute to degenerative processes in the central nervous system (CNS). CCL11 levels increase in the plasma and cerebrospinal fluid of both mice and humans as part of normal aging. In mice, these increases are associated with declining neurogenesis and impaired cognition and memory. In humans, elevated plasma levels of CCL11 have been observed in Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, and secondary progressive multiple sclerosis when compared to age-matched, healthy controls. Since CCL11 is capable of crossing the blood-brain barrier of normal mice, it is plausible that eotaxins generated in the periphery may exert physiological and pathological actions in the CNS. Here, we briefly review known functions of eotaxin family members during innate immunity, and then focus on whether and how these molecules might participate in the progression of neurodegenerative diseases.
Holtom-Garrett Program in Neuroimmunology, Department of Neurology, University of Michigan Medical School, Ann Arbor, MI, USA.
Amanda K
AK
Huber
Holtom-Garrett Program in Neuroimmunology, Department of Neurology, University of Michigan Medical School, Ann Arbor, MI, USA.
David A
DA
Giles
Holtom-Garrett Program in Neuroimmunology, Department of Neurology, University of Michigan Medical School, Ann Arbor, MI, USA.
Benjamin M
BM
Segal
Holtom-Garrett Program in Neuroimmunology, Department of Neurology, University of Michigan Medical School, Ann Arbor, MI, USA. Electronic address: davidira@med.umich.edu.
David N
DN
Irani
D000375:Aging / Q000276:immunology; D000818:Animals; D054413:Chemokine CCL11 / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D054423:Chemokine CCL24 / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D000075906:Chemokine CCL26 / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D019636:Neurodegenerative Diseases / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D054397:Receptors, CCR3 / Q000276:immunology / Q000378:metabolism
D054413:Chemokine CCL11; D054423:Chemokine CCL24; D000075906:Chemokine CCL26; D054397:Receptors, CCR3
Aging; CCL11; Eotaxin; Multiple sclerosis; Neurodegeneration; Neurogenesis