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J Exp Med. 2014 Apr 7;211(4):595-604. doi: 10.1084/jem.20131377. Epub 2014 Mar 10.

T cell-derived interleukin (IL)-21 promotes brain injury following stroke in mice.

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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.


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.

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