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

被引：88

作者：

Clarkson, Benjamin D. S. ^{[1
,3
]}

Ling, Changying ^{[1
]}

Shi, Yejie ^{[2
]}

Harris, Melissa G. ^{[1
,4
]}

Rayasam, Aditya ^{[4
]}

Sun, Dandan ^{[2
,5
]}

Salamat, M. Shahriar ^{[1
]}

Kuchroo, Vijay ^{[6
,7
]}

Lambris, John D. ^{[8
]}

Sandor, Matyas ^{[1
]}

Fabry, Zsuzsanna ^{[1
]}

机构：

[1] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pathol & Lab Med, Madison, WI 53792 USA

[2] Univ Wisconsin, Sch Med & Publ Hlth, Dept Neurol Surg, Madison, WI 53792 USA

[3] Univ Wisconsin, Sch Med & Publ Hlth, Dept Cellular & Mol Pathol, Madison, WI 53792 USA

[4] Univ Wisconsin, Sch Med & Publ Hlth, Neurosci Training Program, Madison, WI 53792 USA

[5] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15213 USA

[6] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA

[7] Harvard Univ, Sch Med, Boston, MA 02115 USA

[8] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2014年 / 211卷 / 04期

基金：

美国国家卫生研究院;

关键词：

ISCHEMIC-STROKE; CEREBRAL-ISCHEMIA; IL-21; LYMPHOCYTES; REJECTION; COUNTERACTS; DYSFUNCTION; EXPRESSION; AUTOIMMUNE; DISEASE;

D O I：

10.1084/jem.20131377

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：595 / 604

页数：10

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