Mucosal surface and skin protection by MHC class I-based immune regulation
基于 MHC I 类的免疫调节保护粘膜表面和皮肤
基本信息
- 批准号:10516738
- 负责人:
- 金额:$ 38.38万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-11-15 至 2024-10-31
- 项目状态:已结题
- 来源:
- 关键词:AblationAdaptive Immune SystemAdoptive TransferAffectAnalgesicsAntibody TherapyAntigen PresentationAntigen-Presenting CellsAntigensAppendicitisBiologyCD4 Positive T LymphocytesCD8-Positive T-LymphocytesCD8B1 geneCell CommunicationCell Differentiation processCell modelCell physiologyCellsChemicalsColitisComplexCre-LoxPCytoprotectionDataDefense MechanismsDiscriminationDiseaseEnvironmentExhibitsFOXP3 geneFutureGenerationsGeneticGenetic TranscriptionGram-Negative BacteriaGut MucosaHLA-A2 AntigenHealthHematopoieticHomeHomeostasisHomingHumanImmuneImmune mediated destructionIn VitroInfectious AgentInflammationInflammatoryInflammatory ResponseInjuryInterventionKnock-outKnowledgeLeadLeucine EnkephalinLigandsLiteratureLymphoidMHC Class I GenesMHC Class II GenesMethionine EnkephalinModelingMolecularMonoclonal AntibodiesMucositisMucous MembraneMusObstructionOperative Surgical ProceduresOpioidOrganOvalbuminPathway interactionsPeptidesPhenotypePlayPopulationPositioning AttributeProcessPublishingRNA InterferenceRUNX3 geneRegulatory T-LymphocyteReportingRoleSignal TransductionSiteSkinSortingSpecificityStromal CellsSurfaceSymbiosisSystemT-Cell ReceptorT-LymphocyteT-Lymphocyte SubsetsTestingThymus GlandTissuesUp-Regulationchemically induced colitiscross reactivitydesigngut microbiotahazardimmunoregulationinflammatory painmelanocytemesenteric lymph nodemicrobialmicrobiotanovelpreproenkephalinproenkephalinreceptorreceptor bindingresponsescavenger receptortherapy designtissue injurytranscriptometranscriptome sequencingwoundwound healing
项目摘要
The exposure of the mucosal surfaces and the skin to the environment subjects these tissues to not only
physical injuries and chemical hazards but also microbial damage and immune destruction. Tissue injuries lead
to cascades of inflammatory responses involving both innate and adaptive immune cells systemically in the
lymphoid system and locally in the nonlymphoid target tissues. A well-orchestrated innate and adaptive
immune regulatory response in inflamed tissues is essential for damage control and wound healing. In the
adaptive branch, the CD8 and CD4 lineages of αβ T cells develop in the thymus based on recognition of
antigens presented by MHC class I (MHCI) and MHC class II (MHCII), respectively, yielding a repertoire that
discriminates self from nonself. In the mucosal surfaces and the skin, the symbiosis with microbiota poses a
challenge to the concept of self and nonself discrimination, as the mutualistic microbiota may not fit into the
traditional definition of self or nonself. In a recently-published study of mucosal immune regulation at the
interface with the gut microbiota, we reported the discovery of a novel subset of T cells, MHCI-restricted
CD4+Foxp3+ regulatory T (CI-Treg) cells. They were generated through cross-differentiation from the CD8
lineage to CD4 T cells in a “selfless” mode and effectively controlled mucosal inflammation. CI-Treg cells
recognize MHCI which is broadly expressed in all nucleated tissue cells and typically presents endogenous
tissue antigens, unlike the standard MHCII-restricted CD4 Treg cells which recognize antigens processed
through the exogenous pathway and presented by rare antigen-presenting cells. Microbiota plays a major role
in the expansion / homeostasis of CI-Treg cells. In humans, MHCI-restricted CD4 T cells were identified long
ago in health or disease conditions. However, how CI-Treg cells are generated and how they function in the
mucosal surfaces and the skin remain largely unknown. Our study with a surgical approach in mice revealed
that the mesenteric lymph nodes — which drain the gut mucosae, but not the thymus, were required for CI-Treg
generation. Interestingly, the generation of CI-Treg cells required MHCII, but the cross-differentiated cells
retained the MHCI-restricted specificity. We will use a combination of surgical, molecular and cellular
approaches to investigate the role of microbial and host signals in generation and homeostatic expansion of
CI-Treg cells. We will also examine the function of CI-Treg cells in protecting the mucosal surfaces and the skin
from chemically-induced inflammatory damage, immune-mediated destruction, or inflammatory injury initiated
by physical obstruction. The knowledge from this study will help design future interventions to control
inflammatory tissue damage in the mucosal surfaces and the skin.
粘膜表面和皮肤暴露在环境中使这些组织不仅
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Lymph Node Stromal Cell-Intrinsic MHC Class II Expression Promotes MHC Class I-Restricted CD8 T Cell Lineage Conversion to Regulatory CD4 T Cells.
- DOI:10.4049/jimmunol.2100396
- 发表时间:2021-09-15
- 期刊:
- 影响因子:0
- 作者:Honan AM;Vazquez EN;Chen Z
- 通讯作者:Chen Z
{{
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 }}
Zhibin Chen其他文献
Zhibin Chen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('Zhibin Chen', 18)}}的其他基金
The role of type 2 inflammation in the initiation and progression of metaplastic differentiation and neoplastic transformation of gastric epithelia
2型炎症在胃上皮化生分化和肿瘤转化的起始和进展中的作用
- 批准号:
10633096 - 财政年份:2020
- 资助金额:
$ 38.38万 - 项目类别:
The role of type 2 inflammation in the initiation and progression of metaplastic differentiation and neoplastic transformation of gastric epithelia
2型炎症在胃上皮化生分化和肿瘤转化的起始和进展中的作用
- 批准号:
10172874 - 财政年份:2020
- 资助金额:
$ 38.38万 - 项目类别:
The role of type 2 inflammation in the initiation and progression of metaplastic differentiation and neoplastic transformation of gastric epithelia
2型炎症在胃上皮化生分化和肿瘤转化的起始和进展中的作用
- 批准号:
10405615 - 财政年份:2020
- 资助金额:
$ 38.38万 - 项目类别:
The role of type 2 inflammation in the initiation and progression of metaplastic differentiation and neoplastic transformation of gastric epithelia
2型炎症在胃上皮化生分化和肿瘤转化的起始和进展中的作用
- 批准号:
10737935 - 财政年份:2020
- 资助金额:
$ 38.38万 - 项目类别:
The role of type 2 inflammation in the initiation and progression of metaplastic differentiation and neoplastic transformation of gastric epithelia
2型炎症在胃上皮化生分化和肿瘤转化的起始和进展中的作用
- 批准号:
10598700 - 财政年份:2020
- 资助金额:
$ 38.38万 - 项目类别:
Mucosal surface and skin protection by MHC class I-based immune regulation
基于 MHC I 类的免疫调节保护粘膜表面和皮肤
- 批准号:
10291421 - 财政年份:2018
- 资助金额:
$ 38.38万 - 项目类别:
Mucosal surface and skin protection by MHC class I-based immune regulation
基于 MHC I 类的免疫调节保护粘膜表面和皮肤
- 批准号:
10053700 - 财政年份:2018
- 资助金额:
$ 38.38万 - 项目类别:
Role of Th1/17 in gastric tumor initiation triggered by CTLA4 dysregulation
Th1/17 在 CTLA4 失调引发的胃肿瘤发生中的作用
- 批准号:
8688191 - 财政年份:2013
- 资助金额:
$ 38.38万 - 项目类别:
Role of Th1/17 in gastric tumor initiation triggered by CTLA4 dysregulation
Th1/17 在 CTLA4 失调引发的胃肿瘤发生中的作用
- 批准号:
8570484 - 财政年份:2013
- 资助金额:
$ 38.38万 - 项目类别:
The quantitative biology of CTLA4 splice variants in T1D
T1D 中 CTLA4 剪接变体的定量生物学
- 批准号:
7798450 - 财政年份:2009
- 资助金额:
$ 38.38万 - 项目类别:
相似海外基金
Single-cell analysis of adaptive immune system cells in IBD patients
IBD 患者适应性免疫系统细胞的单细胞分析
- 批准号:
22KJ2212 - 财政年份:2023
- 资助金额:
$ 38.38万 - 项目类别:
Grant-in-Aid for JSPS Fellows
Antigen presentation to the adaptive immune system in the choroid contributes to ocular autoimmune disease
脉络膜中的适应性免疫系统的抗原呈递导致眼部自身免疫性疾病
- 批准号:
10740465 - 财政年份:2023
- 资助金额:
$ 38.38万 - 项目类别:
Elucidation of the adaptive immune system in teleost fish
阐明硬骨鱼的适应性免疫系统
- 批准号:
22K05824 - 财政年份:2022
- 资助金额:
$ 38.38万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Peripheral Adaptive Immune System Changes Associated with Alzhiemer's Disease
与阿尔茨海默病相关的外周适应性免疫系统变化
- 批准号:
10194864 - 财政年份:2021
- 资助金额:
$ 38.38万 - 项目类别:
Interaction of Galectin-9 and Pregnancy-Specific Glycoprotein 1 in the Regulation of Cells of the Innate and Adaptive Immune System
Galectin-9 和妊娠特异性糖蛋白 1 在先天性和适应性免疫系统细胞调节中的相互作用
- 批准号:
10434937 - 财政年份:2021
- 资助金额:
$ 38.38万 - 项目类别:
Interaction of Galectin-9 and Pregnancy-Specific Glycoprotein 1 in the Regulation of Cells of the Innate and Adaptive Immune System
Galectin-9 和妊娠特异性糖蛋白 1 在先天性和适应性免疫系统细胞调节中的相互作用
- 批准号:
10302501 - 财政年份:2021
- 资助金额:
$ 38.38万 - 项目类别:
Learning a molecular shape space for the adaptive immune system
学习适应性免疫系统的分子形状空间
- 批准号:
10275426 - 财政年份:2021
- 资助金额:
$ 38.38万 - 项目类别:
CAREER: Emergence of Functional Organization in the Adaptive Immune System
职业:适应性免疫系统中功能组织的出现
- 批准号:
2045054 - 财政年份:2021
- 资助金额:
$ 38.38万 - 项目类别:
Continuing Grant
Learning a molecular shape space for the adaptive immune system
学习适应性免疫系统的分子形状空间
- 批准号:
10669709 - 财政年份:2021
- 资助金额:
$ 38.38万 - 项目类别:
Learning a molecular shape space for the adaptive immune system
学习适应性免疫系统的分子形状空间
- 批准号:
10467050 - 财政年份:2021
- 资助金额:
$ 38.38万 - 项目类别:














{{item.name}}会员




