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

Benjamin D.S. Clarkson, Changying Ling, Yejie Shi, Melissa G. Harris, Aditya Rayasam, Dandan Sun, M. Shahriar Salamat, Vijay Kuchroo, John D. Lambris, Matyas Sandor, Zsuzsanna Fabry

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)595-604
Number of pages10
JournalJournal of Experimental Medicine
Issue number4
StatePublished - Apr 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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