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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.

SUBMITTER: Clarkson BD 

PROVIDER: S-EPMC3978271 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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

Clarkson Benjamin D S BD   Ling Changying C   Shi Yejie Y   Harris Melissa G MG   Rayasam Aditya A   Sun Dandan D   Salamat M Shahriar MS   Kuchroo Vijay V   Lambris John D JD   Sandor Matyas M   Fabry Zsuzsanna Z  

The Journal of experimental medicine 20140310 4


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 sta  ...[more]

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