IL-27 and downstream mechanisms in Alopecia Areata
斑秃中的 IL-27 及其下游机制
基本信息
- 批准号:10297577
- 负责人:
- 金额:$ 33.99万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-17 至 2026-08-31
- 项目状态:未结题
- 来源:
- 关键词:20 year oldAddressAdoptedAdoptive TransferAffectAlopecia AreataAnti-Inflammatory AgentsAntigen-Presenting CellsAntiinflammatory EffectAutoimmuneAutoimmune DiseasesAutoimmune ResponsesAutoimmunityAutomobile DrivingBlocking AntibodiesBone MarrowCD8-Positive T-LymphocytesCD8B1 geneCellsCellular biologyClinicalDataDependovirusDevelopmentDiseaseEndothelial CellsEpithelialEpithelial CellsEquilibriumFDA approvedFamiliarityFoundationsGene ExpressionGeneticGoalsHairHair follicle structureImmuneImmune TargetingImmune responseImmune systemInfiltrationInflammatoryInterleukin-10KnowledgeLeadLigandsLigationMHC Class I GenesMHC Class II GenesMaintenanceMediatingMedicalModelingMolecularMusOrganOutcomeParticipantPathogenesisPathogenicityPathway interactionsPatientsPharmaceutical PreparationsPhenotypePopulationProductionPropertyQuality of lifeRegulatory T-LymphocyteResearchRoleSignal PathwaySignal TransductionSiteSkinT cell differentiationT cell responseT-LymphocyteTherapeutic AgentsTherapeutic UsesTissuesUnited StatesUp-RegulationWorkautoimmune pathogenesisautoreactive T cellbasecell typecytokinedraining lymph nodeeffector T cellimmunoregulationimprovedin vivointerleukin-10 receptorlifetime riskmortalitymouse modelnew therapeutic targetnovel strategiesnovel therapeutic interventionoverexpressionpreservationpreventpsychosocialreceptorself esteemside effecttooltranscriptomicstumor
项目摘要
PROJECT SUMMARY
Alopecia areata (AA) is a common autoimmune disease in which the hair follicle is the target of attack
and results clinically in hair loss. Despite the associated high lifetime risk of approximately 2% and its substantive
psychosocial impact, no FDA approved treatments exist for AA. The lack of effective options for the population
that suffers from this disfiguring disease with significant psychosocial ramifications represents a significant unmet
medical need.
The absence of approved treatments is in part due to an incomplete understanding of the unbalanced
equilibrium between pathogenic immune responses and immunoregulatory mechanisms that prevent
autoimmunity in AA. Although many cytokines, pathways, and cell types have been hypothesized to prevent
immune attack of the hair follicle, it is unknown what factors participate in regulating autoimmune responses in
vivo. Identifying these critical immunoregulatory participants may not only deepen our understanding of AA
pathogenesis, but may reveal anti-inflammatory pathways that may be exploited to develop novel approaches to
treatment.
IL-27 is a cytokine with immunoregulatory properties that has been studied in various autoimmune,
infectious, and tumor models. The receptor for IL-27 is expressed by a wide array of immune cell types as well
as epithelial and endothelial cells, supporting its potential to modulate the immune system and critical cell
types that interact with the immune system. In particular, IL-27 has been shown to dampen conventional T cell
responses, increase the number of regulatory T cells, and induce naïve and previously activated CD4 and CD8
T cells to produce IL-10, a well-known cytokine with anti-inflammatory effects in most contexts. Our
preliminary data indicate that overexpression of IL-27 can substantially prevent the development of murine AA,
and further analysis revealed regulatory T cells and IL-10 as potential downstream candidates participating in
disease suppression.
We propose to study the mechanisms of AA suppression of exogenous IL-27 and its downstream
effects on regulating immune responses to the hair follicle and preventing the development of AA. We have
adopted and further developed a spontaneous AA mouse model to robustly develop disease in an inducible,
controlled, and well-characterized manner by adoptive transfer of activated pathogenic T cells. Combining our
AA model with newly developed genetic tools will allow us to dissect the mechanisms by which IL-27 may be
used to ablate AA pathogenesis and has the potential to reveal novel therapeutic strategies.
项目摘要
斑秃(AA)是一种常见的自身免疫性疾病,毛囊是攻击的目标
并在临床上导致脱发。尽管相关的高终身风险约为2%,
心理社会影响,没有FDA批准的AA治疗方法。民众缺乏有效的选择
患有这种具有显著心理社会后果的毁容疾病的人,
医疗需求。
缺乏批准的治疗方法部分是由于对不平衡的
病原性免疫应答和免疫调节机制之间的平衡,
AA的自身免疫性尽管许多细胞因子、途径和细胞类型已经被假设可以预防
毛囊的免疫攻击,它是未知的因素参与调节自身免疫反应,
vivo.识别这些关键的免疫调节参与者不仅可以加深我们对AA的理解,
发病机制,但可能揭示抗炎途径,可用于开发新的方法,
治疗
IL-27是一种具有免疫调节特性的细胞因子,
感染和肿瘤模型。IL-27的受体也由多种免疫细胞类型表达
作为上皮细胞和内皮细胞,支持其调节免疫系统和关键细胞的潜力,
与免疫系统相互作用的类型。特别是,IL-27已经显示出抑制常规T细胞增殖,
反应,增加调节性T细胞的数量,并诱导幼稚和先前活化的CD 4和CD 8
T细胞产生IL-10,一种在大多数情况下具有抗炎作用的众所周知的细胞因子。我们
初步数据表明IL-27的过表达可以基本上防止鼠AA的发展,
进一步的分析显示,调节性T细胞和IL-10是潜在的下游候选者,
疾病抑制
本研究拟探讨AA抑制外源性IL-27及其下游信号转导的机制,
调节毛囊的免疫反应和预防AA的发展。我们有
采用并进一步开发了自发AA小鼠模型,
通过过继转移活化的病原性T细胞,以受控和充分表征的方式。结合我们
使用新开发的遗传工具的AA模型将使我们能够剖析IL-27可能的机制
用于消除AA发病机制,并有可能揭示新的治疗策略。
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 }}
Ali Jabbari其他文献
Ali Jabbari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('Ali Jabbari', 18)}}的其他基金
IL-27 and downstream mechanisms in Alopecia Areata
斑秃中的 IL-27 及其下游机制
- 批准号:
10685308 - 财政年份:2021
- 资助金额:
$ 33.99万 - 项目类别:
IL-27 and downstream mechanisms in Alopecia Areata
IL-27 及其下游机制在斑秃中的作用
- 批准号:
10490304 - 财政年份:2021
- 资助金额:
$ 33.99万 - 项目类别:
Determining the role of T cell effector functions in Alopecia Areata
确定 T 细胞效应功能在斑秃中的作用
- 批准号:
10477192 - 财政年份:2020
- 资助金额:
$ 33.99万 - 项目类别:
Determining the role of T cell effector functions in Alopecia Areata
确定 T 细胞效应功能在斑秃中的作用
- 批准号:
10183173 - 财政年份:2020
- 资助金额:
$ 33.99万 - 项目类别:
Determining the role of T cell effector functions in Alopecia Areata
确定 T 细胞效应功能在斑秃中的作用
- 批准号:
10664944 - 财政年份:2020
- 资助金额:
$ 33.99万 - 项目类别:
Determining the role of T cell effector functions in Alopecia Areata
确定 T 细胞效应功能在斑秃中的作用
- 批准号:
10006640 - 财政年份:2020
- 资助金额:
$ 33.99万 - 项目类别:
Defining T helper cell associated cytokines and mechanisms in Alopecia Areata
斑秃中 T 辅助细胞相关细胞因子和机制的定义
- 批准号:
9979751 - 财政年份:2016
- 资助金额:
$ 33.99万 - 项目类别:
Defining T helper cell associated cytokines and mechanisms in Alopecia Areata
斑秃中 T 辅助细胞相关细胞因子和机制的定义
- 批准号:
9488636 - 财政年份:2016
- 资助金额:
$ 33.99万 - 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:
$ 33.99万 - 项目类别:
Fellowship
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:
$ 33.99万 - 项目类别:
Research Grant
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:
$ 33.99万 - 项目类别:
Continuing 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:
$ 33.99万 - 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:
$ 33.99万 - 项目类别:
Standard Grant
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:
$ 33.99万 - 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:
$ 33.99万 - 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:
$ 33.99万 - 项目类别:
EU-Funded
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:
$ 33.99万 - 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:
$ 33.99万 - 项目类别:
Research Grant