title: T cell-derived interleukin (IL)-21 promotes brain injury following stroke in mice.
abstract: T lymphocytes are key contributors to the acute phase of cerebral ischemia reperfusion injury, but the relevant T cell-derived mediators of tissue injury remain unknown. Using a mouse model of transient focal brain ischemia, we report that IL-21 is highly up-regulated in the injured mouse brain after cerebral ischemia. IL-21-deficient mice have smaller infarcts, improved neurological function, and reduced lymphocyte accumulation in the brain within 24 h of reperfusion. Intracellular cytokine staining and adoptive transfer experiments revealed that brain-infiltrating CD4(+) T cells are the predominant IL-21 source. Mice treated with decoy IL-21 receptor Fc fusion protein are protected from reperfusion injury. In postmortem human brain tissue, IL-21 localized to perivascular CD4(+) T cells in the area surrounding acute stroke lesions, suggesting that IL-21-mediated brain injury may be relevant to human stroke.
authors.affiliation: Department of Pathology and Laboratory Medicine, 2 Department of Neurological Surgery, 3 Department of Cellular and Molecular Pathology, 4 Neuroscience Training Program, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53792.
authors.forename: Benjamin D S
authors.initials: BD
authors.lastname: Clarkson
authors.forename: Changying
authors.initials: C
authors.lastname: Ling
authors.forename: Yejie
authors.initials: Y
authors.lastname: Shi
authors.forename: Melissa G
authors.initials: MG
authors.lastname: Harris
authors.forename: Aditya
authors.initials: A
authors.lastname: Rayasam
authors.forename: Dandan
authors.initials: D
authors.lastname: Sun
authors.forename: M Shahriar
authors.initials: MS
authors.lastname: Salamat
authors.forename: Vijay
authors.initials: V
authors.lastname: Kuchroo
authors.forename: John D
authors.initials: JD
authors.lastname: Lambris
authors.forename: Matyas
authors.initials: M
authors.lastname: Sandor
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Fabry
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002544:Cerebral Infarction / Q000150:complications / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020244:Infarction, Middle Cerebral Artery; D007378:Interleukins / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D013194:Staining and Labeling; D020521:Stroke / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation; D000098546:Interleukin-21
chemical_list: D015704:CD4 Antigens; D007378:Interleukins; D000098546:Interleukin-21