MyD88 is essential to sustain mTOR activation necessary to promote T helper 17 cell proliferation by linking IL-1 and IL-23 signaling

JiHoon Chang; Burkett P.R.; Borges C.M.Kuchroo V.K.Turka L.A.Chang C.-H.

首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >MyD88 is essential to sustain mTOR activation necessary to promote T helper 17 cell proliferation by linking IL-1 and IL-23 signaling

【24h】

MyD88 is essential to sustain mTOR activation necessary to promote T helper 17 cell proliferation by linking IL-1 and IL-23 signaling

机译：MyD88 is essential to sustain mTOR activation necessary to promote T helper 17 cell proliferation by linking IL-1 and IL-23 signaling

获取原文

获取原文并翻译 | 示例

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相关主题

摘要

Myeloid differentiation primary response protein 88 (MyD88) is classically known as an adaptor, linking TLR and IL-1R to downstream signaling pathways in the innate immune system. In addition to its role in innate immune cells, MyD88 has been shown to play an important role in T cells. How MyD88 regulates helper T-cell differentiation remains largely unknown, however. Here we demonstrate that MyD88 is an important regulator of IL-17-producing CD4~+ T helper cells (Th17) cell proliferation. MyD88-deficient CD4~+ T cells showed a defect in Th17 cell differentiation, but not in Th1 cell or Th2 cell differentiation. The impaired IL-17 production from MyD88-deficient CD4 ~+ T cells is not a result of defective RAR-related orphan receptor _γt (ROR_γt) expression. Instead, MyD88 is essential for sustaining the mammalian target of rapamycin (mTOR) activation necessary to promote Th17 cell proliferation by linking IL-1 and IL-23 signaling. MyD88-deficient CD4~+ T cells showed impaired mTOR activation and, consequently, reduced Th17 cell proliferation. Importantly, the absence of MyD88 in T cells ameliorated disease in the experimental autoimmune encephalomyelitis model. Taken together, our results demonstrate that MyD88 has a dual function in Th17 cells by delivering IL-1 signaling during the early differentiation stage and integrating IL-23 signaling to the mTOR complex to expand committed Th17 cells.

著录项

来源
《Proceedings of the National Academy of Sciences of the United States of America》 |2013年第6期|2270-2275|共6页
作者
JiHoon Chang; Burkett P.R.; Borges C.M.Kuchroo V.K.Turka L.A.Chang C.-H.;
展开▼
作者单位

Transplant Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States;

Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, United States;

Center for Neurologic Diseases, Boston, MA 02115, United StatesDepartment of Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02129, United States;

展开▼
收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词

MyD88 is essential to sustain mTOR activation necessary to promote T helper 17 cell proliferation by linking IL-1 and IL-23 signaling

摘要

著录项

相关主题

期刊订阅