Photodermatological Effects of Toll Like Receptor-4 (TLR4)

Toll 样受体 4 (TLR4) 的光皮肤效应

基本信息

  • 批准号:
    8107559
  • 负责人:
  • 金额:
    $ 7.03万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-06-01 至 2013-05-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Ultraviolet B (UVB) radiation is a potent immunosuppressive agent that inhibits cell-mediated immune responses. The mechanisms by which UVB radiation influences cell-mediated immune responses have been the subject of extensive investigation. However, there is little information on the role of innate immunity in this process. Toll-like receptors (TLRs), one component of innate immunity, are intricately associated with a number of dermatologic conditions. Our recent experiments suggest that certain components of innate immunity, especially TLR4, may play an important role in photoimmunosuppression. Using gene knockout mice, we have found that TLR4 causes UVB- induced suppression of allergic contact hypersensitivity. We have also found that CD8+ T-cells that secrete IFN-3 are effector cells of contact hypersensitivity in wild type C57BL/6 mice, whereas CD8+ T-cells that secrete IL-17 are the primary effector cells for contact hypersensitivity in TLR4 gene knockout mice. UV-induced regulatory T-cells act to inhibit the development and/or function of IFN-3 producing T-cells but not IL-17 producing T-cells. Since TLR4 deficiency directs the cell-mediated immune response towards IL-17 producing T-cells, the inability of UV-induced regulatory T-cells to inhibit IL-17 producing cells results in prevention of immunosuppression in TLR4 gene knockout mice. In this study, we will assess whether regulatory T-cells develop in TLR4 gene knockout mice after UVB radiation exposure, and, if so, characterize their phenotype and cytokine profile. We will also determine why regulatory T-cells either do not develop or are non-functional in TLR4 gene knockout mice. This study will provide useful data to evaluate the role of TLR4 in UVB induced immunosuppression. The ultimate goal of this project is to identify specific molecules that can be targeted for prevention and/or treatment. PUBLIC HEALTH RELEVANCE: Ultraviolet B (UVB) radiation is well known to cause skin cancers which develop when the capability of our immune system is suppressed thus facilitating growth of these tumors. In this proposal, I will perform extensive studies in mice to evaluate the mechanisms through which Toll like receptor-4 (TLR4), a key component of innate immunity, mediates immunosuppression that occurs following UVB radiation. This may allow us to identify genetic loci that are involved in UVB-induced immune suppression and to develop immunopreventive and immunotherapeutic approaches for photoimmunosuppression.
描述(由申请方提供):紫外线B(UVB)辐射是一种有效的免疫抑制剂,可抑制细胞介导的免疫应答。UVB辐射影响细胞介导的免疫反应的机制一直是广泛研究的主题。然而,关于先天免疫在这一过程中的作用的信息很少。Toll样受体(TLR)是先天免疫的一个组成部分,与许多皮肤病密切相关。我们最近的实验表明,先天免疫的某些成分,特别是TLR 4,可能在光免疫抑制中发挥重要作用。使用基因敲除小鼠,我们发现TLR 4导致UVB诱导的过敏性接触性超敏反应的抑制。我们还发现,分泌IFN-3的CD 8 + T细胞是野生型C57 BL/6小鼠中接触性超敏反应的效应细胞,而分泌IL-17的CD 8 + T细胞是TLR 4基因敲除小鼠中接触性超敏反应的主要效应细胞。UV诱导的调节性T细胞用于抑制产生IFN-3的T细胞而不是产生IL-17的T细胞的发育和/或功能。由于TLR 4缺陷将细胞介导的免疫应答导向产生IL-17的T细胞,因此UV诱导的调节性T细胞不能抑制产生IL-17的细胞导致防止TLR 4基因敲除小鼠中的免疫抑制。在这项研究中,我们将评估是否调节性T细胞开发TLR 4基因敲除小鼠UVB辐射暴露后,如果是这样,其表型和细胞因子的特点。我们还将确定为什么调节性T细胞在TLR 4基因敲除小鼠中不发育或无功能。本研究为探讨TLR 4在UVB诱导的免疫抑制中的作用提供了有用的数据。该项目的最终目标是确定可用于预防和/或治疗的特定分子。 公共卫生关系:众所周知,紫外线B(UVB)辐射会导致皮肤癌,当我们的免疫系统受到抑制时,皮肤癌就会发生,从而促进这些肿瘤的生长。在这个提议中,我将在小鼠中进行广泛的研究,以评估Toll样受体4(TLR 4),先天免疫的关键组成部分,介导UVB辐射后发生的免疫抑制的机制。这可能使我们能够确定参与UVB诱导的免疫抑制的遗传位点,并开发用于光免疫抑制的免疫预防和免疫抑制方法。

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Regulation of ultraviolet radiation induced cutaneous photoimmunosuppression by toll-like receptor-4.
  • DOI:
    10.1016/j.abb.2011.01.005
  • 发表时间:
    2011-04-15
  • 期刊:
  • 影响因子:
    3.9
  • 作者:
    Lewis W;Simanyi E;Li H;Thompson CA;Nasti TH;Jaleel T;Xu H;Yusuf N
  • 通讯作者:
    Yusuf N
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Nabiha Yusuf其他文献

Nabiha Yusuf的其他文献

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{{ truncateString('Nabiha Yusuf', 18)}}的其他基金

Mechanisms elicited by type I interferons in cutaneous photocarcinogenesis
I 型干扰素引起皮肤光致癌的机制
  • 批准号:
    10019328
  • 财政年份:
    2016
  • 资助金额:
    $ 7.03万
  • 项目类别:
Mechanisms elicited by type I interferons in cutaneous photocarcinogenesis
I 型干扰素引起皮肤光致癌的机制
  • 批准号:
    9764280
  • 财政年份:
    2016
  • 资助金额:
    $ 7.03万
  • 项目类别:
Mechanisms elicited by type I interferons in cutaneous photocarcinogenesis
I 型干扰素引起皮肤光致癌的机制
  • 批准号:
    9238330
  • 财政年份:
    2016
  • 资助金额:
    $ 7.03万
  • 项目类别:
Photodermatological Effects of Toll Like Receptor-4 (TLR4)
Toll 样受体 4 (TLR4) 的光皮肤效应
  • 批准号:
    7879788
  • 财政年份:
    2010
  • 资助金额:
    $ 7.03万
  • 项目类别:
Role of the Innate Immune System in Regulation of UVB Induced Skin Carcinogenesis
先天免疫系统在调节 UVB 诱导的皮肤癌发生中的作用
  • 批准号:
    7677175
  • 财政年份:
    2009
  • 资助金额:
    $ 7.03万
  • 项目类别:
The Innate Immune System in Regulation of DVB Induced Skin Carcinogenesis
先天免疫系统调节 DVB 诱导的皮肤癌发生
  • 批准号:
    7691492
  • 财政年份:
    2008
  • 资助金额:
    $ 7.03万
  • 项目类别:

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