期刊
BLOOD
卷 108, 期 5, 页码 1595-1601出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2006-04-015016
关键词
-
类别
资金
- NHLBI NIH HHS [R01 HL077177] Funding Source: Medline
- NIAID NIH HHS [AI45515, AI50837] Funding Source: Medline
- NIDDK NIH HHS [T32DK007519] Funding Source: Medline
IL-23, an IL-12-related cytokine, induces an IL-17-secreting T-helper phenotype that is involved in autoimmune diseases and host defense against certain pathogens. Although the transcription factors required for development of IL-23-stimulated cells are unknown, we show that T-bet is a critical negative regulator of the IL-23-primed T-cell phenotype, which we term Th1 beta. Th1 or Th1 beta Tbx21(-/-) cultures secrete higher than WT levels of IL-17 in response to T-cell receptor (TCR) or IL-23 + IL-18 stimulation. Ectopic T-bet expression in Th1 beta cells promotes IFN-gamma secretion but decreases IL-17 production. Although antigen-receptor stimulation of Th1 beta cells stimulates IL-17 production, it also induces the IFN-gamma-independent expression of T-bet and progression to a Th1 cytokine secretion pattern. T-bet is required for the progression to the Th1 phenotype, because Tbx21(-/-) Th1 beta cultures maintain the IL-17-secreting phenotype after 2 weeks of culture. Addition of IFN-gamma to Tbx21(-/-) Th1 beta cultures cannot recover the progression to the Th1 phenotype, suggesting T-bet, rather than IFN-gamma, mediates Th1 beta to Th1 progression. The transient nature of the Th1 beta phenotype suggests that these cells are a component of type I immunity and that T-bet expression is a critical determinant of Thi versus Th1 beta cell fate.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据