2009年8月
Pivotal role of cerebral interleukin-17-producing gamma delta T cells in the delayed phase of ischemic brain injury
NATURE MEDICINE
- 巻
- 15
- 号
- 8
- 開始ページ
- 946
- 終了ページ
- U150
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1038/nm.1999
- 出版者・発行元
- NATURE PUBLISHING GROUP
Lymphocyte recruitment and activation have been implicated in the progression of cerebral ischemia-reperfusion (I/R) injury, but the roles of specific lymphocyte subpopulations and cytokines during stroke remain to be clarified. Here we demonstrate that the infiltration of T cells into the brain, as well as the cytokines interleukin-23 (IL-23) and IL-17, have pivotal roles in the evolution of brain infarction and accompanying neurological deficits. Blockade of T cell infiltration into the brain by the immunosuppressant FTY720 reduced I/R-induced brain damage. The expression of IL-23, which was derived mostly from infiltrated macrophages, increased on day 1 after I/R, whereas IL-17 levels were elevated after day 3, and this induction of IL-17 was dependent on IL-23. These data, together with analysis of mice genetically disrupted for IL-17 and IL-23, suggest that IL-23 functions in the immediate stage of I/R brain injury, whereas IL-17 has an important role in the delayed phase of I/R injury during which apoptotic neuronal death occurs in the penumbra. Intracellular cytokine staining revealed that gamma delta T lymphocytes, but not CD4(+) helper T cells, were a major source of IL-17. Moreover, depletion of gamma delta T lymphocytes ameliorated the I/R injury. We propose that T lymphocytes, including gamma delta T lymphocytes, could be a therapeutic target for mitigating the inflammatory events that amplify the initial damage in cerebral ischemia.
- リンク情報
- ID情報
-
- DOI : 10.1038/nm.1999
- ISSN : 1078-8956
- PubMed ID : 19648929
- Web of Science ID : WOS:000268770400040