TY - JOUR
T1 - T cell-derived interleukin (IL)-21 promotes brain injury following stroke in mice
AU - Clarkson, Benjamin D.S.
AU - Ling, Changying
AU - Shi, Yejie
AU - Harris, Melissa G.
AU - Rayasam, Aditya
AU - Sun, Dandan
AU - Salamat, M. Shahriar
AU - Kuchroo, Vijay
AU - Lambris, John D.
AU - Sandor, Matyas
AU - Fabry, Zsuzsanna
PY - 2014/4
Y1 - 2014/4
N2 - 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.
AB - 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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U2 - 10.1084/jem.20131377
DO - 10.1084/jem.20131377
M3 - Article
C2 - 24616379
AN - SCOPUS:84897945825
SN - 0022-1007
VL - 211
SP - 595
EP - 604
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 4
ER -