Skip to main content

感谢您访问Nature.com。您正在使用浏览器版本，其中支持CSS有限。为了获得最佳体验，我们建议您使用更新的浏览器（或在Internet Explorer中关闭兼容模式）。与此同时，为了确保继续支持，我们在没有样式和JavaScript的情况下显示该网站。

A critical role for NF-κB ingata3.expression and TH2在过敏气道炎症中的分化

自然免疫学体积2那页面45–50 (2001年的）引用这篇文章

Abstract

The transcription factor GATA-3 is expressed in T helper 2 (TH2的）but not TH1cells and plays a critical role in TH2differentiation and allergic airway inflammationin vivo。缺乏核因子κB（NF-κB）的P50亚基的小鼠无法安装气道嗜酸性炎症。我们在这里展示这不是由于t的缺陷H2cell recruitment but due to the inability of the p50−/−小鼠生产白细胞介素4（IL-4），IL-5和IL-13：细胞因子，其在哮喘发病机制中起着不同的作用。CD4.+T cells from p50−/−小鼠未能诱导gata3.expression under TH2-differentiating conditions but showed unimpaired T-bet expression and interferon γ (IFN-γ) production under TH1-differentiating conditions. Inhibition of NF-κB activity prevented GATA-3 expression and TH2cytokine production in developing, but not committed, TH2cells. Our studies provide a molecular basis for the need for both T cell receptor and cytokine signaling for GATA-3 expression and, in turn, TH2differentiation.

这是订阅内容的预览

Access options

买文章

在ReadCube上获取时间限制或全文访问。

$32.00

Buy

All prices are NET prices.

Figure 1: p50−/−mice can recruit adoptively transferred TH2cells to generate airway inflammation.
Figure 2: NF-κB–deficiency impairs GATA-3 expression.
Figure 3: GATA-3 expression in developing TH2个细胞需要NF-κB活化。
图4：GATA-3表达或T不需要NF-κBH2cytokine production in committed TH2cells.
Figure 5: NF-κB–deficiency does not affect T-bet expression and IFN-γ production.

References

  1. Walker，C.等。过敏和非过敏性哮喘学具有外周血和支气管肺泡灌洗的T细胞活化和细胞因子产生的不同模式。是。Rev. Respir。解释。146，109-115（1992）。

    CASArticleGoogle Scholar

  2. 罗宾逊，D.S.等。特应性哮喘的主要Th2样支气管肺泡T淋巴细胞群。n.ngl。J.Med。326那29.8.–304 (1992).

    CASArticleGoogle Scholar

  3. Wills-Karp, M. Immunologic basis of antigen-induced airway hyperresponsiveness.安努。Rev.Immunol。17.那255–281 (1999).

    CASArticleGoogle Scholar

  4. 射线，A.＆Cohn，L.Th2细胞和哮喘中的GATA-3：对气道炎症调节的新见解。J. Clin。投资。104，985-993。（1999）。

    CASArticleGoogle Scholar

  5. Zhang, D.-H., Cohn, L., Ray, P., Bottomly, K. & Ray, A. Transcription factor GATA-3 is differentially expressed in Th1 and Th2 cells and controls Th2-specific expression of the interleukin-5 gene.J. Biol。化学。27.2，21597-21603（1997）。

    CASArticleGoogle Scholar

  6. Zheng, W.-P. & Flavell, R. A. The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells.细胞8.9.那587–596 (1997).

    CASArticleGoogle Scholar

  7. Ting, C.-N。那Olson, M. C., Barton, K. P. & Leiden, J. M. Transcription factor GATA-3 is required for development of the T-cell lineage.Nature384那474–478. (1996).

    CASArticleGoogle Scholar

  8. 张，D。等人。通过表达GATA-3的显性阴性突变体抑制哮喘小鼠模型中的过敏性炎症。免疫11，473-482。（1999）。

    CASArticleGoogle Scholar

  9. Baldwin，A.S.JR NF-κB和IκB蛋白质：新发现和见解。安努。Rev.Immunol。14，649-681（1996）。

    CASArticleGoogle Scholar

  10. Sha, W. C. Regulation of immune responses by NF-κB/Rel transcription factors.J. Exp。医学。18.7.那143–146 (1998).

    CASArticleGoogle Scholar

  11. 杨，L.等。核因子κB在过敏气道炎症中嗜酸性粒细胞凋亡中的核因子κB的基本作用。J. Exp。医学。18.8.，1739-1750。（1998）。

    CASArticleGoogle Scholar

  12. Cohn, L., Homer, R. J., Marinov, A., Rankin, J. & Bottomly, K. Induction of airway mucus production by T helper 2 (Th2) cells: a critical role for interleukin-4 in cell recruitment but not mucus production.J. Exp。医学。18.6那17.37–1747 (1997).

    CASArticleGoogle Scholar

  13. Cohn, L., Tepper, J. S. & Bottomly, K. IL-4-independent induction of airway hyperresponsiveness by Th2, but not Th1, cells.J. Immunol.1613813-3816。（1998）。

    CASPubMedGoogle Scholar

  14. Ouyang, W. et al. Inhibition of Th1 development mediated by GATA-3 through an IL-4-independent mechanism.免疫9.那7.45–755. (1998).

    CASArticleGoogle Scholar

  15. Agarwal, S. & Rao, A. Modulation of chromatin structure regulates cytokine gene expression during T cell differentiation.免疫9.那7.65–775. (1998).

    CASArticleGoogle Scholar

  16. Siegel，M. D.，Zhang，D.-h.，雷，P.＆Ray，A.在鼠EL-4细胞中营地激活白细胞介素-5启动子需要GATA-3和CLE0元素。J. Biol。化学。27.0，24548-24555（1995）。

    CASArticleGoogle Scholar

  17. Zhang, D.-H., Yang, L. & Ray, A. Differential responsiveness of the interleukin-5 (IL-5) and IL-4 genes to transcription factor GATA-3.J. Immunol.161那3817–3821 (1998).

    CASPubMedGoogle Scholar

  18. Ranganath，S.等人。GATA-3依赖性增强剂活性IL-4基因调节。J. Immunol.161那3822–3826 (1998).

    CASPubMedPubMed CentralGoogle Scholar

  19. Agarwal，S.，Avni，O.＆Rao，A.细胞型限制转录因子NFAT与远端IL-4增强剂的结合in vivo。免疫12那643–652 (2000).

    CASArticleGoogle Scholar

  20. George, K. M. et al. Embryonic expression and cloning of the murine GATA-3 gene.Development120，2673-2686。（1994）。

    CASPubMedGoogle Scholar

  21. Ouyang, W. et al. Stat6-independent GATA-3 autoactivation directs IL-4-independent Th2 development and commitment.免疫12那27.–37 (2000).

    CASArticleGoogle Scholar

  22. Ranger, A. M. et al. The transcription factor NF-ATc is essential for cardiac valve formation.Nature392那18.6–190 (1998).

    CASArticleGoogle Scholar

  23. Yoshida, H. et al. The transcription factor NF-ATc1 regulates lymphocyte proliferation and Th2 cytokine production.免疫8.，115-124（1998）。

    CASArticleGoogle Scholar

  24. Lin, Y. Z., Yao, S. Y., Veach, R. A., Torgerson, T. R. & Hawiger, J. Inhibition of nuclear translocation of transcription factor NF-κB by a synthetic peptide containing a cell membrane-permeable motif and nuclear localization sequence.J. Biol。化学。27.0那14255–14258 (1995).

    CASArticleGoogle Scholar

  25. Liu, R. Y., Fan, C., Olashaw, N. E., Wang, X. & Zuckerman, K. S. Tumor necrosis factor-α-induced proliferation of human Mo7e leukemic cells occurs通过activation of nuclear factor κB transcription factor.J. Biol。化学。27.4，13877-13885（1999）。

    CASArticleGoogle Scholar

  26. McKenzie，A. N.等。人和小鼠IL-13基因的结构比较和染色体定位。J. Immunol.150，5436-5444（1993）。

    CASPubMedGoogle Scholar

  27. Szabo, S. J. et al. A novel transcription factor, T-bet, directs Th1 lineage commitment.细胞100那655–669 (2000).

    CASArticleGoogle Scholar

  28. Jain，J.，Loh，C.＆Rao，A. IL-2基因的转录调节。Curr. Opin. Immunol.7.，333-342（1995）。

    CASArticleGoogle Scholar

  29. Kuo, C. T. & Leiden, J. M. Transcriptional regulation of T lymphocyte development and function.安努。Rev.Immunol。17.那149–187 (1999).

    CASArticleGoogle Scholar

  30. Jamieson, C., McCaffrey, P. G., Rao, A. & Sen, R. Physiologic activation of T cells通过the T cell receptor induces NF-κB.J. Immunol.147，416-420（1991）。

    CASPubMedGoogle Scholar

  31. Kang, S.-M., Tran, A.-C., Grilli, M. & Lenardo, M. J. NF-κB subunit regulation in nontransformed CD4+T淋巴细胞。Science256，1451-1456（1992）。

    ArticleGoogle Scholar

  32. Robinson, D. et al. IGIF does not drive Th1 development but synergizes with IL-12 for interferon-gamma production and activates IRAK and NF-κB.免疫7.那571–581 (1997).

    CASArticleGoogle Scholar

  33. Matsumoto, S. et al. Interleukin-18 activates NF-κB in murine T helper type 1 cells.Biochem. Biophys. Res. Commun.234那454–457 (1997).

    CASArticleGoogle Scholar

  34. Sica，A.等人。NF-κB和NFAT与干扰素-γ启动子的相互作用。J. Biol。化学。27.2那30412–30420 (1997).

    CASArticleGoogle Scholar

  35. Murphy，T.L，克利夫兰，M.G.，Kulesza，P.，Magram，J.＆Murphy，K.M。通过NF-κB半场通过NF-κB的Intereheukin 12 p40的调节。摩尔。细胞。BIOL。15那5258–5267 (1995).

    CASArticleGoogle Scholar

  36. Shen, C. H. & Stavnezer, J. Interaction of stat6 and NF-κB: direct association and synergistic activation of interleukin-4-induced transcription.摩尔。细胞。BIOL。18.，3395-3404（1998）。

    CASArticleGoogle Scholar

  37. Delphin, S. & Stavnezer, J. Characterization of an interleukin 4 (IL-4) responsive region in the immunoglobulin heavy chain germline epsilon promoter: regulation by NF- IL-4, a C/EBP family member and NF-κB/p50.J. Exp。医学。18.1，181-192（1995）。

    CASArticleGoogle Scholar

  38. Mikita, T., Campbell, D., Wu, P., Williamson, K. & Schindler, U. Requirements for interleukin-4-induced gene expression and functional characterization of Stat6.摩尔。细胞。BIOL。16，5811-5820（1996）。

    CASArticleGoogle Scholar

  39. Sha, W. C., Liou, H.-C., Tuomanen, E. I. & Baltimore, D. Targeted disruption of the p50 subunit of NF-κB leads to multifocal defects in immune responses.细胞8.0，321-330（1995）。

    CASArticleGoogle Scholar

下载参考资料

Acknowledgements

We thank L. Glimcher for the antibody to T-bet. Supported by grants from the NIH (to A. R.).

作者信息

Affiliations

  1. Department of Medicine, Pulmonary and Critical Care Section, Yale University School of Medicine, 333 Cedar Street, LCI 105, New Haven, CT 06520, USA

    jyoti das.那长鸿辰那溧阳阳那Lauren Cohn, Prabir Ray & Anuradha Ray

作者
  1. jyoti das.
    View author publications

    You can also search for this author inPubMedGoogle Scholar

  2. 长鸿辰
    View author publications

    You can also search for this author inPubMedGoogle Scholar

  3. 溧阳阳
    View author publications

    You can also search for this author inPubMedGoogle Scholar

  4. Lauren Cohn
    View author publications

    You can also search for this author inPubMedGoogle Scholar

  5. Prabir Ray
    View author publications

    You can also search for this author inPubMedGoogle Scholar

  6. Anuradha Ray.
    View author publications

    You can also search for this author inPubMedGoogle Scholar

Corresponding author

Correspondence toAnuradha Ray.。

权利和权限

Reprints and Permissions

关于this article

引用这篇文章

Das, J., Chen, CH., Yang, L.等等。A critical role for NF-κB ingata3.expression and TH2在过敏气道炎症中的分化。Nat Immunol2那45–50 (2001). https://doi.org/10.1038/83158

Download citation

  • 已收到：

  • 公认：

  • Issue Date：

  • 迪伊：https://doi.org/10.1038/83158

进一步阅读

Search

高级搜索

快速链接

自然简报

注册自然简报时事通讯 - 每天都有什么事，免费到您的收件箱。

Get the most important science stories of the day, free in your inbox. 注册自然简报