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首页> 外文期刊>Nature immunology >A p85 alpha-osteopontin axis couples the receptor ICOS to sustained Bcl-6 expression by follicular helper and regulatory T cells
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A p85 alpha-osteopontin axis couples the receptor ICOS to sustained Bcl-6 expression by follicular helper and regulatory T cells

机译:P85α-骨桥蛋白轴将受体ICOS与滤泡助手和调节性T细胞携带持续的Bcl-6表达

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摘要

Follicular helper T cells (T-FH cells) and follicular regulatory T cells (T-FR cells) regulate the quantity and quality of humoral immunity. Although both cell types express the costimulatory receptor ICOS and require the transcription factor Bcl-6 for their differentiation, the ICOS-dependent pathways that coordinate their responses are not well understood. Here we report that activation of ICOS in CD4(+) T cells promoted interaction of the p85 alpha regulatory subunit of the signaling kinase PI(3)K and intracellular osteopontin (OPN-i), followed by translocation of OPN-i to the nucleus, its interaction with Bcl-6 and protection of Bcl-6 from ubiquitin-dependent proteasome degradation. Post-translational protection of Bcl-6 by OPN-i was essential for sustained responses of T-FH cells and T-FR cells and regulation of the germinal center B cell response to antigen. Thus, the p85 alpha-OPN-i axis represents a molecular bridge that couples activation of ICOS to Bcl-6-dependent functional differentiation of T-FH cells and T-FR cells; this suggests new therapeutic avenues to manipulate the responses of these cells.
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著录项

  • 来源
    《Nature immunology》 |2015年第1期|共13页
  • 作者单位

    Dana Farber Canc Inst Dept Canc Immunol &

    AIDS Boston MA 02115 USA;

    Dana Farber Canc Inst Dept Canc Immunol &

    AIDS Boston MA 02115 USA;

    Dana Farber Canc Inst Dept Canc Immunol &

    AIDS Boston MA 02115 USA;

    Dana Farber Canc Inst Dept Canc Immunol &

    AIDS Boston MA 02115 USA;

    Dana Farber Canc Inst Dept Canc Immunol &

    AIDS Boston MA 02115 USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 医学免疫学;
  • 关键词

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