Effector-Regulator Immune Interactions During Autoimmune Demyelinating Disease

自身免疫性脱髓鞘疾病期间效应器-调节器免疫相互作用

基本信息

  • 批准号:
    10359998
  • 负责人:
  • 金额:
    --
  • 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:
    2022-01-01 至 2026-12-31
  • 项目状态:
    未结题

项目摘要

Multiple sclerosis (MS) is an inflammatory, demyelinating disorder of the central nervous system (CNS) that affects over 1 million people in the US. T-cell-driven immunopathology is a central feature of MS and other immune-mediated diseases. As a consequence, the immune regulation of these pathogenic T-cell responses is an important quest in the approach to autoimmunity. We have had a long-standing interest in the immune basis of human multiple sclerosis (MS) and its animal model (EAE). While the pathogenic role of CD4 T-cells is well established in these diseases, there is growing evidence from us and others for a role of CD8 T-cells in these diseases. Through studies in MS and EAE, we have demonstrated the critical disease regulatory role of CD8 T-cells in disease. Similar appreciation for the role of these cells in downregulating other autoimmune diseases has also emerged. We have also shown that the suppressor activity of MS relapse-associated CD8 T-cells can be restored by in vitro pre-treatment with specific cytokines, revealing functional plasticity of these cells and providing a potential avenue for therapeutic intervention. At the same time, it is also becoming clear that severe autoimmune disease is characterized by increased resistance of effector/pathogenic CD4 T-cells to immune regulation. Collectively, these studies underscore the importance of understanding both the biology of CD4 effector T-cell resistance to suppression as well as the intricacies of CD8 suppression and its modulation. Our proposal addresses this poorly understood but fundamental feature of the immune regulatory apparatus, in the context of MS. Our recent studies demonstrate several novel aspects of the CD4-CD8 effector-regulator dynamics and based on these findings, we hypothesize that CD4 T-cells from MS patients have an intrinsically enhanced tendency to develop effector resistance to immune suppression in an inflammatory context, while CD8 T-cells from MS patients have an intrinsically enhanced tendency to develop lower suppressive ability. We also hypothesize that these phenotypes are plastic and can be modulated by appropriate stimuli. To address these hypotheses, we will use a two-pronged approach: (1) We will address the biology and modulation of CD4 resistance in MS to gain direct insights into these processes in the context of autoimmune disease. A part of this aim will also focus on the novel CD4-intrinsic biology of IL-17 cytokines, as demonstrated in our recent publication; and (2) We will also address the biology and modulation of CD8 suppression in MS. These studies will provide important insights into the immune dysregulation that underlies MS pathogenesis, with implications for treatment approaches in MS and multiple other disease settings.
多发性硬化(MS)是中枢神经系统(CNS)的炎性脱髓鞘疾病, 影响了美国超过一百万人。T细胞驱动的免疫病理学是MS和其他疾病的中心特征。 免疫介导的疾病。因此,这些致病性T细胞应答的免疫调节是 是研究自身免疫的重要探索我们对免疫基础的兴趣由来已久 人多发性硬化症(MS)及其动物模型(EAE)。虽然CD 4 T细胞的致病作用是很好的 在这些疾病中建立,我们和其他人越来越多的证据表明CD 8 T细胞在这些疾病中的作用。 疾病通过在MS和EAE中的研究,我们已经证明了CD 8的关键疾病调节作用, 疾病中的T细胞对这些细胞在下调其他自身免疫性疾病中的作用的类似认识, 疾病也出现了。我们还发现MS复发相关的CD 8抑制剂活性, T细胞可以通过用特异性细胞因子进行体外预处理来恢复,揭示了T细胞的功能可塑性。 这些细胞,并提供了一个潜在的治疗干预途径。同时,也是 越来越清楚的是,严重的自身免疫性疾病的特点是增加的抵抗力, 效应/致病性CD 4 T细胞对免疫调节的影响。总的来说,这些研究强调了 理解CD 4效应T细胞对抑制的抵抗的生物学以及 CD 8抑制及其调节的复杂性。我们的建议没有很好地解决这个问题 在MS的背景下,我们理解免疫调节装置的基本特征。 最近的研究证明了CD 4-CD 8效应-调节动力学的几个新方面, 根据这些发现,我们假设MS患者的CD 4 T细胞具有内在增强的倾向, 在炎症背景下,CD 8 T细胞对免疫抑制产生效应抵抗,而来自MS的CD 8 T细胞 患者具有发展较低抑制能力的内在增强趋势。我们还假设 这些表型是可塑的,可以通过适当的刺激来调节。为了解决这些假设, 我们将采用双管齐下的方法:(1)我们将研究MS中CD 4抗性的生物学和调节 在自身免疫性疾病的背景下直接了解这些过程。这一目标的一部分还将 专注于IL-17细胞因子的新型CD 4内在生物学,如我们最近的出版物所示;和(2) 我们还将讨论MS中CD 8抑制的生物学和调制。 重要的见解免疫失调,MS发病机制的基础,与影响 MS和多种其他疾病环境中的治疗方法。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

NITIN J KARANDIKAR其他文献

NITIN J KARANDIKAR的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('NITIN J KARANDIKAR', 18)}}的其他基金

Effector-Regulator Immune Interactions During Autoimmune Demyelinating Disease
自身免疫性脱髓鞘疾病期间效应器-调节器免疫相互作用
  • 批准号:
    10595509
  • 财政年份:
    2022
  • 资助金额:
    --
  • 项目类别:
ShEEP Request for Cytek Aurora Spectral Flow Cytometer
ShEEP 请求 Cytek Aurora 光谱流式细胞仪
  • 批准号:
    9905780
  • 财政年份:
    2019
  • 资助金额:
    --
  • 项目类别:
Immunotherapeutic Regulatory CD8 T cells in Autoimmune Demyelinating Disease
自身免疫性脱髓鞘疾病中的免疫治疗调节性 CD8 T 细胞
  • 批准号:
    9338988
  • 财政年份:
    2017
  • 资助金额:
    --
  • 项目类别:
Immunotherapeutic Regulatory CD8 T cells in Autoimmune Demyelinating Disease
自身免疫性脱髓鞘疾病中的免疫治疗调节性 CD8 T 细胞
  • 批准号:
    9483533
  • 财政年份:
    2017
  • 资助金额:
    --
  • 项目类别:
Immunotherapeutic Regulatory CD8 T cells in Autoimmune Demyelinating Disease
自身免疫性脱髓鞘疾病中的免疫治疗调节性 CD8 T 细胞
  • 批准号:
    10248844
  • 财政年份:
    2017
  • 资助金额:
    --
  • 项目类别:
Immunotherapeutic Regulatory CD8 T cells in Autoimmune Demyelinating Disease
自身免疫性脱髓鞘疾病中的免疫治疗调节性 CD8 T 细胞
  • 批准号:
    10447061
  • 财政年份:
    2017
  • 资助金额:
    --
  • 项目类别:
Immune Dysregulation During Multiple Sclerosis Relapse
多发性硬化症复发期间的免疫失调
  • 批准号:
    9929670
  • 财政年份:
    2016
  • 资助金额:
    --
  • 项目类别:
Immune Dysregulation During Multiple Sclerosis Relapse
多发性硬化症复发期间的免疫失调
  • 批准号:
    9915848
  • 财政年份:
    2016
  • 资助金额:
    --
  • 项目类别:
CNS-Specific Regulatory CD8+ T Cells in Autoimmune Demyelination
CNS 特异性调节 CD8 T 细胞在自身免疫性脱髓鞘中的作用
  • 批准号:
    8627103
  • 财政年份:
    2011
  • 资助金额:
    --
  • 项目类别:
CNS-Specific Regulatory CD8+ T Cells in Autoimmune Demyelination
CNS 特异性调节 CD8 T 细胞在自身免疫性脱髓鞘中的作用
  • 批准号:
    8648996
  • 财政年份:
    2011
  • 资助金额:
    --
  • 项目类别:

相似海外基金

Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
  • 批准号:
    MR/S03398X/2
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Fellowship
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
  • 批准号:
    2338423
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Continuing Grant
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
  • 批准号:
    EP/Y001486/1
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Research Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
  • 批准号:
    MR/X03657X/1
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
  • 批准号:
    2348066
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
  • 批准号:
    AH/Z505481/1
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10107647
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
  • 批准号:
    2341402
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10106221
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
  • 批准号:
    AH/Z505341/1
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了