Clarkson, Benjamin D.S.Ling, ChangyingShi, YejieHarris, Melissa G.Rayasam, AdityaSun, DandanSalamat, M. ShahriarKuchroo, VijayLambris, John D.Sandor, MatyasFabry, Zsuzsanna2014-11-032014Clarkson, B. D., C. Ling, Y. Shi, M. G. Harris, A. Rayasam, D. Sun, M. S. Salamat, et al. 2014. “T cell–derived interleukin (IL)-21 promotes brain injury following stroke in mice.” The Journal of Experimental Medicine 211 (4): 595-604. doi:10.1084/jem.20131377. http://dx.doi.org/10.1084/jem.20131377.0022-1007http://nrs.harvard.edu/urn-3:HUL.InstRepos:13347540T 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.en-USJournal Article2014-11-0310.1084/jem.20131377