Interleukin-17 in post-stroke neurodegeneration.
Stroke is a leading cause of physical disability with neurodegenerative sequelae such as dementia and depression causing significant excess morbidity. Stroke severity can be exacerbated by apoptotic cell death in ischemic tissue, of which inflammatory activity is a key determinant. Studies have identified harmful and beneficial sets of T lymphocytes that infiltrate the brain post-stroke and their activation signals, suggesting that they might be targeted for therapeutic benefit. Animal models and human studies implicate interleukin(IL)-17 and its congeners (e.g. IL-23, IL-21) as mediators of tissue damage in the delayed phase of the inflammatory cascade and the involvement of T lymphocytes in propagating IL-17 release. In this review, we highlight the current understanding of IL-17 secreting cells, including sets of CD4(+) αβ and CD4(-) γδ T lymphocytes, as potentially important mediators of brain pathology post-stroke. Interactions between the IL-17 axis and innate pathways, positive feedback mechanisms that prolong or amplify IL-17, and IL-17 regulatory pathways may offer intervention targets to enhance recovery, prevent long-term decline, and improve quality of life.
Neuropsychopharmacology Research Group, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario M4N 3M5, Canada.
Walter
W
Swardfager
Daniel A
DA
Winer
Nathan
N
Herrmann
Shawn
S
Winer
Krista L
KL
Lanctôt
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D020521:Stroke / Q000150:complications / Q000276:immunology / Q000378:metabolism*
D020381:Interleukin-17