Invited Review

Journal of Neuroimmune Pharmacology

, Volume 4, Issue 4, pp 462-475

Open Access This content is freely available online to anyone, anywhere at any time.

CNS Infiltration of Peripheral Immune Cells: D-Day for Neurodegenerative Disease?

  • Kavon Rezai-ZadehAffiliated withDepartment of Biomedical Sciences, Cedars-Sinai Medical Center
  • , David GateAffiliated withDepartment of Neurosurgery, Maxine Dunitz Neurosurgical Institute
  • , Terrence TownAffiliated withDepartment of Biomedical Sciences, Cedars-Sinai Medical CenterDepartment of Neurosurgery, Maxine Dunitz Neurosurgical InstituteDepartment of Medicine, David Geffen School of Medicine, University of CaliforniaDepartment of Neurosurgery, Cedars-Sinai Medical Center Email author 

Abstract

While the central nervous system (CNS) was once thought to be excluded from surveillance by immune cells, a concept known as “immune privilege,” it is now clear that immune responses do occur in the CNS—giving rise to the field of neuroimmunology. These CNS immune responses can be driven by endogenous (glial) and/or exogenous (peripheral leukocyte) sources and can serve either productive or pathological roles. Recent evidence from mouse models supports the notion that infiltration of peripheral monocytes/macrophages limits progression of Alzheimer's disease pathology and militates against West Nile virus encephalitis. In addition, infiltrating T lymphocytes may help spare neuronal loss in models of amyotrophic lateral sclerosis. On the other hand, CNS leukocyte penetration drives experimental autoimmune encephalomyelitis (a mouse model for the human demyelinating disease multiple sclerosis) and may also be pathological in both Parkinson's disease and human immunodeficiency virus encephalitis. A critical understanding of the cellular and molecular mechanisms responsible for trafficking of immune cells from the periphery into the diseased CNS will be key to target these cells for therapeutic intervention in neurodegenerative diseases, thereby allowing neuroregenerative processes to ensue.

Keywords

brain central nervous system neuroinflammation neuroimmunology leukocyte lymphocyte regulatory T cell monocyte macrophage cytokine chemokine transforming growth factor tumor necrosis factor interleukin-17 interleukin-23 Alzheimer's disease Parkinson's disease West Nile encephalitis multiple sclerosis experimental autoimmune encephalomyelitis human immunodeficiency virus amyotrophic lateral sclerosis