Regulation of bone loss by IL-23/IL-17A axis in inflammatory arthritis

IL-23/IL-17A 轴对炎性关节炎中骨丢失的调节

基本信息

项目摘要

DESCRIPTION (provided by applicant): About 50 million Americans (22%) suffer from some form of arthritis and estimates are that, with the aging population worldwide, 67 million adults will have arthritis by 2030 with an economic impact higher than $128 billion dollars. Although interleukin-23 (IL-23) has been implicated in the pathogenesis of arthritis, the molecular mechanisms remain unknown. Since the discovery of IL-23 regulation of pathogenic T helper cells that express interleukin-17 (Th17) the importance of direct actions of IL-23 in arthritis is overshadowed. To highlight its importance we developed gene-transfer models of IL-23 and IL-17A and using these models we established that IL-23 is a potent inducer of arthritis, independently of IL-17A. Dissection of IL-23 from the IL- 23/IL-17A axis has allowed us to uncover novel mechanisms of myeloid cell activation previously overlooked. We identified that IL-23 induces arthritis independently of Th17 cells and through activation of myeloid cells. T cells and myeloid cells share a requirement for costimulatory signals that are mediated by ITAMs. The ITAM is a conserved signaling motif contained in the cytoplasmic domain of transmembrane adaptor molecules that are associated and transmit signals from various immunoreceptors present in haematopoietic progenitors. These signals orchestrate synovial inflammation and differentiation of myeloid cells to bone resorbing cells called osteoclasts. Discovering the cellular and molecular mechanisms that dictate recruitment and activation of osteoclasts in inflammatory arthritis is central to preventing this disabling condition. Detailed understanding of these cellular and molecular interactions will yield insights into regulation of arthritis that can be exploited for therapeutic interventions.
描述(由申请人提供):大约5000万美国人(22%)患有某种形式的关节炎,据估计,随着全球人口老龄化,到2030年,将有6700万成年人患有关节炎,经济影响将超过1280亿美元。虽然白细胞介素-23 (IL-23)与关节炎的发病机制有关,但其分子机制尚不清楚。自从发现IL-23调节表达白细胞介素-17 (interleukin-17, Th17)的致病性T辅助细胞以来,IL-23在关节炎中的直接作用的重要性被掩盖了。为了强调其重要性,我们开发了IL-23和IL-17A的基因转移模型,并利用这些模型建立了IL-23是一种有效的关节炎诱导剂,独立于IL-17A。从IL-23 /IL- 17a轴上分离IL-23使我们发现了以前被忽视的髓细胞活化的新机制。我们发现IL-23诱导关节炎独立于Th17细胞,并通过激活髓细胞。T细胞和髓细胞对itam介导的共刺激信号有共同的需求。ITAM是一个保守的信号基序,包含在跨膜接头分子的细胞质域中,该分子与造血祖细胞中存在的各种免疫受体相关并传递信号。这些信号协调滑膜炎症和髓细胞分化为骨吸收细胞,称为破骨细胞。发现炎症性关节炎中决定破骨细胞募集和激活的细胞和分子机制是预防这种致残状况的核心。对这些细胞和分子相互作用的详细了解将产生对关节炎调节的见解,可以用于治疗干预。

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 }}

Iannis Elias Adamopoulos其他文献

Iannis Elias Adamopoulos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('Iannis Elias Adamopoulos', 18)}}的其他基金

Immune mechanisms of pain of the IL-23IL-17 Axis in Inflammatory Arthritis
炎症性关节炎中 IL-23IL-17 轴疼痛的免疫机制
  • 批准号:
    10861492
  • 财政年份:
    2023
  • 资助金额:
    $ 32.92万
  • 项目类别:
The IL-23/IL-17 Axis in Inflammatory Arthritis
炎症性关节炎中的 IL-23/IL-17 轴
  • 批准号:
    10413524
  • 财政年份:
    2021
  • 资助金额:
    $ 32.92万
  • 项目类别:
The IL-23/IL-17 Axis in Inflammatory Arthritis
炎症性关节炎中的 IL-23/IL-17 轴
  • 批准号:
    10307090
  • 财政年份:
    2021
  • 资助金额:
    $ 32.92万
  • 项目类别:
The IL-23/IL-17 Axis in Inflammatory Arthritis
炎症性关节炎中的 IL-23/IL-17 轴
  • 批准号:
    10529133
  • 财政年份:
    2021
  • 资助金额:
    $ 32.92万
  • 项目类别:
The IL-23/IL-17 Axis in Inflammatory Arthritis
炎症性关节炎中的 IL-23/IL-17 轴
  • 批准号:
    10077832
  • 财政年份:
    2020
  • 资助金额:
    $ 32.92万
  • 项目类别:
The IL-23/IL-17 Axis in Inflammatory Arthritis
炎症性关节炎中的 IL-23/IL-17 轴
  • 批准号:
    10449669
  • 财政年份:
    2020
  • 资助金额:
    $ 32.92万
  • 项目类别:
The IL-23/IL-17 Axis in Inflammatory Arthritis
炎症性关节炎中的 IL-23/IL-17 轴
  • 批准号:
    9763801
  • 财政年份:
    2020
  • 资助金额:
    $ 32.92万
  • 项目类别:
Role of splicing factor SRSF1 in T cell function and autoimmunity
剪接因子 SRSF1 在 T 细胞功能和自身免疫中的作用
  • 批准号:
    10093179
  • 财政年份:
    2016
  • 资助金额:
    $ 32.92万
  • 项目类别:
Regulation of bone loss by IL-23/IL-17A axis in inflammatory arthritis
IL-23/IL-17A 轴对炎性关节炎中骨丢失的调节
  • 批准号:
    8734726
  • 财政年份:
    2013
  • 资助金额:
    $ 32.92万
  • 项目类别:
Regulation of bone loss by IL-23/IL-17A axis in inflammatory arthritis
IL-23/IL-17A 轴对炎性关节炎中骨丢失的调节
  • 批准号:
    8824488
  • 财政年份:
    2012
  • 资助金额:
    $ 32.92万
  • 项目类别:

相似海外基金

Co-designing a lifestyle, stop-vaping intervention for ex-smoking, adult vapers (CLOVER study)
为戒烟的成年电子烟使用者共同设计生活方式、戒烟干预措施(CLOVER 研究)
  • 批准号:
    MR/Z503605/1
  • 财政年份:
    2024
  • 资助金额:
    $ 32.92万
  • 项目类别:
    Research Grant
RAPID: Affective Mechanisms of Adjustment in Diverse Emerging Adult Student Communities Before, During, and Beyond the COVID-19 Pandemic
RAPID:COVID-19 大流行之前、期间和之后不同新兴成人学生社区的情感调整机制
  • 批准号:
    2402691
  • 财政年份:
    2024
  • 资助金额:
    $ 32.92万
  • 项目类别:
    Standard Grant
Early Life Antecedents Predicting Adult Daily Affective Reactivity to Stress
早期生活经历预测成人对压力的日常情感反应
  • 批准号:
    2336167
  • 财政年份:
    2024
  • 资助金额:
    $ 32.92万
  • 项目类别:
    Standard Grant
Elucidation of Adult Newt Cells Regulating the ZRS enhancer during Limb Regeneration
阐明成体蝾螈细胞在肢体再生过程中调节 ZRS 增强子
  • 批准号:
    24K12150
  • 财政年份:
    2024
  • 资助金额:
    $ 32.92万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Migrant Youth and the Sociolegal Construction of Child and Adult Categories
流动青年与儿童和成人类别的社会法律建构
  • 批准号:
    2341428
  • 财政年份:
    2024
  • 资助金额:
    $ 32.92万
  • 项目类别:
    Standard Grant
Understanding how platelets mediate new neuron formation in the adult brain
了解血小板如何介导成人大脑中新神经元的形成
  • 批准号:
    DE240100561
  • 财政年份:
    2024
  • 资助金额:
    $ 32.92万
  • 项目类别:
    Discovery Early Career Researcher Award
Laboratory testing and development of a new adult ankle splint
新型成人踝关节夹板的实验室测试和开发
  • 批准号:
    10065645
  • 财政年份:
    2023
  • 资助金额:
    $ 32.92万
  • 项目类别:
    Collaborative R&D
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
  • 批准号:
    23K09542
  • 财政年份:
    2023
  • 资助金额:
    $ 32.92万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Identification of new specific molecules associated with right ventricular dysfunction in adult patients with congenital heart disease
鉴定与成年先天性心脏病患者右心室功能障碍相关的新特异性分子
  • 批准号:
    23K07552
  • 财政年份:
    2023
  • 资助金额:
    $ 32.92万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Issue identifications and model developments in transitional care for patients with adult congenital heart disease.
成人先天性心脏病患者过渡护理的问题识别和模型开发。
  • 批准号:
    23K07559
  • 财政年份:
    2023
  • 资助金额:
    $ 32.92万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了