Immune Privilege, Müller cells, and Autophagy

免疫特权、Müller 细胞和自噬

基本信息

  • 批准号:
    10501886
  • 负责人:
  • 金额:
    $ 43.18万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-09-01 至 2026-06-30
  • 项目状态:
    未结题

项目摘要

Abstract Immune privilege is a term applied to organs such as the eye that have a unique relationship with the immune response. These sites prohibit the spread of inflammation since even minor episodes can threaten vision. The breakdown of immune privilege is thought to have serious consequences for the eye; however, in spite its powerful influence on inflammation we know little about how immune privilege influences retinal diseases. Müller cells are the major glial cell of the retina that maintain structural integrity. They react in virtually every eye disease but are strikingly resistant damage; importantly they can suppress inflammation. Based on this they should be key participants in immune privilege, but this is not understood. The biological process of autophagy (literally self-eating) is a recycling system that destroys inflammation-inducing cellular debris to prevent tissue damage. Because immune privilege, Müller cells, and autophagy all have anti- inflammatory properties, we will test the novel hypothesis that Müller glial cells utilize the autophagy pathway to support the anti-inflammatory nature of the eye (i.e. immune privilege). We will do this by examining intraocular inflammation in 2 well-characterized disease models, endotoxin induced uveitis (EIU) and experimental autoimmune uveitis (EAU), utilizing mice with autophagy-deficient retinal Müller cells. Since EIU is mediated by the innate arm of the immune system and EAU is an antigen specific T cell mediated disease we will get thorough understanding as to how Müller cell autophagy influences different types of immune mediated diseases of the eye. In Aim 1 we will assess the intraocular inflammatory response in these models by comparing control mice with mice that have had the essential autophagy genes Atg5 and Fip200 deleted specifically in Müller glial cells. We will evaluate inflammatory infiltrates, cytokine production, and retinal integrity in both models. Preliminary data suggests that inflammation and retinal damage are enhanced in the presence of autophagy deficient Müller cells in both models. In Aim 2 we will we will define the molecular basis of these enhanced inflammatory response to determine the contribution of autophagy to immunoregulatory properties of Müller cells in the eye. Studies will include scRNA-seq analysis, examination of the blood retinal barrier, analysis of the T-cell response in EAU, and morphological analysis. In Aim 3 we will test the idea that autophagy supports phagocytosis in Müller cells promoting their anti-inflammatory properties using the process of LC3-associated phagocytosis (or LAP). We will test whether LAP recovers a portion of the vitamin A for the Müller visual cycle. By elucidating the role of Müller cells and autophagy in immune privilege we will better understand their influence on ocular inflammatory responses. Thus, rather than just treating inflammation, we could consider upregulating immune privilege alone, or in combination with other treatments, to target retinal disease.
摘要

项目成果

期刊论文数量(0)
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Thomas Almon Ferguson其他文献

Thomas Almon Ferguson的其他文献

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{{ truncateString('Thomas Almon Ferguson', 18)}}的其他基金

Modulation of cone photoreceptor function by autophagy
自噬调节视锥光感受器功能
  • 批准号:
    10681018
  • 财政年份:
    2023
  • 资助金额:
    $ 43.18万
  • 项目类别:
Immune Privilege, Müller cells, and Autophagy
免疫特权、Müller 细胞和自噬
  • 批准号:
    10680566
  • 财政年份:
    2022
  • 资助金额:
    $ 43.18万
  • 项目类别:
Regulation of Immunity by Dead Cells
死亡细胞对免疫的调节
  • 批准号:
    7060799
  • 财政年份:
    2005
  • 资助金额:
    $ 43.18万
  • 项目类别:
Regulation of Immunity by Dead Cells
死亡细胞对免疫的调节
  • 批准号:
    6878288
  • 财政年份:
    2005
  • 资助金额:
    $ 43.18万
  • 项目类别:
Regulation of Immunity by Dead Cells
死亡细胞对免疫的调节
  • 批准号:
    7409557
  • 财政年份:
    2005
  • 资助金额:
    $ 43.18万
  • 项目类别:
REGULATION OF IMMUNITY BY DEAD CELLS
死亡细胞对免疫的调节
  • 批准号:
    8056821
  • 财政年份:
    2005
  • 资助金额:
    $ 43.18万
  • 项目类别:
Regulation of Immunity by Dead Cells
死亡细胞对免疫的调节
  • 批准号:
    7852063
  • 财政年份:
    2005
  • 资助金额:
    $ 43.18万
  • 项目类别:
Regulation of Immunity by Dead Cells
死亡细胞对免疫的调节
  • 批准号:
    7221200
  • 财政年份:
    2005
  • 资助金额:
    $ 43.18万
  • 项目类别:
CORE-MOLECULAR BIOLOGY
核心分子生物学
  • 批准号:
    6949368
  • 财政年份:
    2005
  • 资助金额:
    $ 43.18万
  • 项目类别:
REGULATION OF IMMUNITY BY DEAD CELLS
死亡细胞对免疫的调节
  • 批准号:
    8244504
  • 财政年份:
    2005
  • 资助金额:
    $ 43.18万
  • 项目类别:

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