The role of circadian clock proteins in innate and adaptive immunity

生物钟蛋白在先天性和适应性免疫中的作用

基本信息

项目摘要

ABSTRACT Within each mammalian cell is a core set of circadian clock proteins that regulate the cellular biology supporting more complex organ physiologies. The central nervous system, entrained by the principle environmental cue – light, synchronizes these peripheral cellular ‘clocks’ across the entire organism, which enables the host organism to anticipate and prepare for the stresses of the active day (e.g., metabolic demands, septic threat). The current evidence, including data derived from our own research program, highlight the profound influence individual clock proteins have on the physiologic capacity with which an organism responds to stress. We first identified that the spectrum of light is a critical determinant of its effects on mammalian biology, and that the short wavelength visible blue spectrum favorably modifies the biology and outcome of sepsis. In murine models of intraabdominal sepsis and Klebsiella pneumoniae (KP) pneumonia, exposure to blue light after sepsis enhanced immune competence, as evidenced by more efficient clearance of bacteria from the septic focus, reduced bacterial dissemination, and attenuated systemic inflammation. The mechanism involved an optic-cholinergic pathway that induced the clock protein Rev-Erba in immune tissues of the spleen and Mj. A Rev-Erba agonist similarly enhance immune function in both in vitro and in vivo studies. Our overarching hypothesis is that the cellular state of the clock protein Rev-Erba is a critical determinant of immune competence and can be modulated to improve the outcome of sepsis. We specifically hypothesize that Rev-Erba regulates the protein machinery supporting the immune phenotype of the mononuclear phagocyte and B cell and is vital to an efficient immune response to microbial threat. In Aim 1 we will study the physiologic and cellular mechanisms by which blue light and the clock protein Rev-Erba regulate monocyte recruitment to the spleen and peripheral tissues and differentiation into a type of monocyte highly efficient in bacterial clearance, using a model of KP pneumonia. In Aim 2, we will explore the mechanisms by which blue light and Rev-Erba modulate B cell PI3K-AKT-mTOR signaling and actin assembly to mediate B cell differentiation, activation, MHC II antigen presentation, and antibody production. As these mechanisms are metabolically demanding and ATP-dependent, we will (Aim 3) determine the mechanisms by which Rev-Erba modulates mitochondrial dynamics to support oxidative metabolism and thereby the phenotype of immune cells during sepsis. The ramifications of light on health and disease remain to be convincingly defined. This proposal will define the biological mechanisms through which circadian clock proteins beneficially alter the host response to acute infectious insult. We will define the dimensions of light and state of clock proteins that are optimally protective and examine their biological relevance and potential therapeutic value in studies of patients with pneumonia.
摘要

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 }}

MATTHEW Randall ROSENGART其他文献

MATTHEW Randall ROSENGART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('MATTHEW Randall ROSENGART', 18)}}的其他基金

The role of circadian clock proteins in innate and adaptive immunity
生物钟蛋白在先天性和适应性免疫中的作用
  • 批准号:
    10892546
  • 财政年份:
    2022
  • 资助金额:
    $ 37.36万
  • 项目类别:
Calcium homeostasis and cellular fitness in sepsis
脓毒症中的钙稳态和细胞适应性
  • 批准号:
    10892600
  • 财政年份:
    2022
  • 资助金额:
    $ 37.36万
  • 项目类别:
CaMK: central regulators of the inflammatory response to surgical sepsis
CaMK:手术败血症炎症反应的中央调节因子
  • 批准号:
    8516525
  • 财政年份:
    2009
  • 资助金额:
    $ 37.36万
  • 项目类别:
CaMK: Central Regulators of the response to Surgical Sepsis
CaMK:手术败血症反应的中央监管者
  • 批准号:
    9043106
  • 财政年份:
    2009
  • 资助金额:
    $ 37.36万
  • 项目类别:
CaMK: Central Regulators of the response to Surgical Sepsis
CaMK:手术败血症反应的中央监管者
  • 批准号:
    9407788
  • 财政年份:
    2009
  • 资助金额:
    $ 37.36万
  • 项目类别:
CaMK: central regulators of the inflammatory response to surgical sepsis
CaMK:手术败血症炎症反应的中央调节因子
  • 批准号:
    8308620
  • 财政年份:
    2009
  • 资助金额:
    $ 37.36万
  • 项目类别:
CaMK: central regulators of the inflammatory response to surgical sepsis
CaMK:手术败血症炎症反应的中央调节因子
  • 批准号:
    7906839
  • 财政年份:
    2009
  • 资助金额:
    $ 37.36万
  • 项目类别:
CaMK: central regulators of the inflammatory response to surgical sepsis
CaMK:手术败血症炎症反应的中央调节因子
  • 批准号:
    8114205
  • 财政年份:
    2009
  • 资助金额:
    $ 37.36万
  • 项目类别:

相似海外基金

Elucidation of acute poisoning mechanism due to abuse of CB1 receptor agonist.
阐明滥用 CB1 受体激动剂引起的急性中毒机制。
  • 批准号:
    21K17323
  • 财政年份:
    2021
  • 资助金额:
    $ 37.36万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Elucidation of acute poisoning mechanism due to abuse of CB1 receptor agonist.
阐明滥用 CB1 受体激动剂引起的急性中毒机制。
  • 批准号:
    19K19485
  • 财政年份:
    2019
  • 资助金额:
    $ 37.36万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Tissue repair effect in acute myocardial infarction through mobilization of endogenous Muse cells by sphingosine-1-phosphate receptor 2 agonist
1-磷酸鞘氨醇受体2激动剂动员内源性Muse细胞对急性心肌梗死的组织修复作用
  • 批准号:
    18K15843
  • 财政年份:
    2018
  • 资助金额:
    $ 37.36万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
EFFECT OF ACUTE E PROSTAGLANDIN AGONIST N BAL EICO
急性 E 型前列腺素激动剂 N BAL EICO 的作用
  • 批准号:
    6115624
  • 财政年份:
    1998
  • 资助金额:
    $ 37.36万
  • 项目类别:
EFFECT OF ACUTE E PROSTAGLANDIN AGONIST N BAL EICO
急性 E 型前列腺素激动剂 N BAL EICO 的作用
  • 批准号:
    6219539
  • 财政年份:
    1998
  • 资助金额:
    $ 37.36万
  • 项目类别:
EFFECT OF ACUTE E PROSTAGLANDIN AGONIST N BAL EICO
急性 E 型前列腺素激动剂 N BAL EICO 的作用
  • 批准号:
    6276858
  • 财政年份:
    1997
  • 资助金额:
    $ 37.36万
  • 项目类别:
ACUTE CHRONIC HORMONAL CHANGES WITH LHRH-AGONIST THERAPY
LHRH 激动剂治疗引起的急性慢性荷尔蒙变化
  • 批准号:
    6250152
  • 财政年份:
    1997
  • 资助金额:
    $ 37.36万
  • 项目类别:
ACUTE CHRONIC HORMONAL CHANGES WITH LHRH-AGONIST THERAPY
LHRH 激动剂治疗引起的急性慢性荷尔蒙变化
  • 批准号:
    6279945
  • 财政年份:
    1997
  • 资助金额:
    $ 37.36万
  • 项目类别:
EFFECT OF ACUTE E PROSTAGLANDIN AGONIST N BAL EICO
急性 E 型前列腺素激动剂 N BAL EICO 的作用
  • 批准号:
    6246787
  • 财政年份:
    1997
  • 资助金额:
    $ 37.36万
  • 项目类别:
PSYCHOPHARMACOLOGY OF DA AGONIST CNS EFFECTS: ACUTE AND CHRONIC STUDIES
DA 激动剂中枢神经系统影响的精神药理学:急性和慢性研究
  • 批准号:
    3891471
  • 财政年份:
  • 资助金额:
    $ 37.36万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了