Reprogramming of tissue structural cells by cutaneous CD4+ T cells
皮肤 CD4 T 细胞对组织结构细胞的重编程
基本信息
- 批准号:10608777
- 负责人:
- 金额:$ 64.57万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-04-19 至 2028-03-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAtopic DermatitisB-LymphocytesBehaviorCD4 Positive T LymphocytesCell Culture SystemCell physiologyCellsChemicalsCutaneousDevelopmentDiseaseDrug TargetingEndothelial CellsEpigenetic ProcessFibroblastsFibrosisFunctional disorderGenetic TranscriptionHost DefenseHumanImmuneIn VitroInfectionInflammationInflammatoryInflammatory ResponseIrritantsKnowledgeLinkMediatorMemoryModalityModificationMonitorOrganismPathway interactionsPatientsPre-Clinical ModelProcessPruritusPsoriasisResolutionSamplingSignal TransductionSiteSkinStimulusSystemT cell responseT-LymphocyteTherapeuticTissue SampleTissuesTraumaUltraviolet RaysVascular Endothelial Cellcell behaviorcytokinehumanized mousein vivoinnovationkeratinocytemicrobialmouse modelnovelnovel therapeuticspathogenpre-clinicalpreventprogramsresponseskin barrierskin disordertargeted treatmenttissue repairtissue-repair responses
项目摘要
Project Summary/Abstract
Although long thought to be a unique feature of adaptive cells such as T and B cells, it is now clear that tissue
structural cells can also harbor ‘memory’ of prior inflammatory responses in the form of stable epigenetic
modifications that alter their transcriptional potential and behavior following subsequent tissue damage, and
this is referred to as ‘inflammatory memory’. This highlights key gaps in our knowledge of T cell-tissue cross-
talk that this proposal seeks to address. The premise of this proposal is that cutaneous T cells reprogram local
keratinocytes and fibroblasts during inflammation, thereby altering their transcriptional and epigenetic
landscape, function, and responses to subsequent stimuli, and that this influences the course and resolution of
inflammatory skin disease. To fill these key knowledge gaps, we will examine the cross-talk between T cell and
structural cells in innovative cell culture systems to monitor changes in cell behavior and function, and
mechanistically link them to transcriptional and epigenetic reprogramming by T cell-derived cytokines. We will
also leverage an established and highly manipulatable murine model of T cell-dependent skin inflammation to
examine the development of inflammatory memory in KCs and Fibs in vivo, to mechanistically identify
important cytokines and epigenetic mediators, and to assess the functional consequences on subsequent
inflammatory and tissue-repair responses. Finally, we will analyze signatures of inflammatory memory in tissue
samples from patients with the common skin inflammatory diseases psoriasis and atopic dermatitis, and
assess epigenetic reprogramming in a preclinical model as a new therapeutic modality to reset inflammatory
memory and break the inflammatory cycle in the skin of these patients.
项目总结/摘要
虽然长期以来被认为是适应性细胞如T和B细胞的独特特征,但现在清楚的是,
结构细胞也可以以稳定的表观遗传方式对先前的炎症反应进行“记忆”,
在随后的组织损伤后改变其转录潜力和行为的修饰,以及
这被称为“炎症性记忆”。这突出了我们对T细胞-组织交叉的认识中的关键差距,
这是该提案试图解决的问题。这个提议的前提是皮肤T细胞局部重编程,
角质形成细胞和成纤维细胞在炎症过程中,从而改变其转录和表观遗传
景观,功能和对后续刺激的反应,这影响了课程和解决方案,
炎症性皮肤病。为了填补这些关键的知识空白,我们将研究T细胞和
创新细胞培养系统中的结构细胞,以监测细胞行为和功能的变化,以及
机械地将它们与T细胞衍生的细胞因子的转录和表观遗传重编程联系起来。我们将
还利用已建立的和高度可操作的T细胞依赖性皮肤炎症小鼠模型,
检查体内KCs和Fib中炎症记忆的发展,
重要的细胞因子和表观遗传介质,并评估功能后果,对后续
炎症和组织修复反应。最后,我们将分析组织中炎症记忆的特征,
来自患有常见皮肤炎性疾病银屑病和特应性皮炎的患者的样品,和
在临床前模型中评估表观遗传重编程作为一种新的治疗方式来重置炎症
并打破这些患者皮肤中的炎症循环。
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)
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Daniel J Campbell其他文献
133 CARDIAC PERFORMANCE, EXERCISE CAPACITY AND PULMONARY FUNCTION AFTER FONTAN SURGERY
Fontan 手术后心脏功能、运动能力和肺功能
- DOI:
10.1203/00006450-198504000-00163 - 发表时间:
1985-04-01 - 期刊:
- 影响因子:3.100
- 作者:
David G Ruschhaupt;Daniel J Campbell;Otto G Thilenius;Robert L Replogle;Rene A Arcilla - 通讯作者:
Rene A Arcilla
Evaluating YouTube Videos on Facelift Surgery for Facial Rejuvenation as a Resource for Patients
评估有关面部年轻化整容手术的 YouTube 视频作为患者的资源
- DOI:
10.1177/00034894231154410 - 发表时间:
2023 - 期刊:
- 影响因子:0
- 作者:
Zachary T Elliot;Joseph S Lu;Daniel J Campbell;Kevin B Xiao;Vanessa Christopher;Howard Krein;R. Heffelfinger - 通讯作者:
R. Heffelfinger
Differences in Functional and Survival Outcomes Between Patients Receiving Primary Surgery vs Chemoradiation Therapy for Treatment of T1-T2 Oropharyngeal Squamous Cell Carcinoma.
接受初次手术与放化疗治疗 T1-T2 口咽鳞状细胞癌的患者功能和生存结果的差异。
- DOI:
10.1001/jamaoto.2023.1944 - 发表时间:
2023 - 期刊:
- 影响因子:0
- 作者:
Dev R Amin;R. Philips;Dylan G Bertoni;Eric V Mastrolonardo;Daniel J Campbell;A. Agarwal;Sruti Tekumalla;Zachary D Urdang;A. Luginbuhl;D. Cognetti;Joseph M. Curry - 通讯作者:
Joseph M. Curry
Evaluating ChatGPT responses on thyroid nodules for patient education.
评估 ChatGPT 对甲状腺结节的反应以进行患者教育。
- DOI:
10.1089/thy.2023.0491 - 发表时间:
2023 - 期刊:
- 影响因子:0
- 作者:
Daniel J Campbell;Leonard E Estephan;Elliott Sina;Eric V Mastrolonardo;Rahul Alapati;Dev R Amin;Elizabeth Cottrill - 通讯作者:
Elizabeth Cottrill
Evaluating ChatGPT Responses on Atrial Fibrillation for Patient Education
评估 ChatGPT 对心房颤动的反应以进行患者教育
- DOI:
10.7759/cureus.61680 - 发表时间:
2024 - 期刊:
- 影响因子:0
- 作者:
Thomas J Lee;Daniel J Campbell;Abhinav K Rao;Afif Hossain;Omar Elkattawy;Navid Radfar;Paul Lee;Julius M Gardin - 通讯作者:
Julius M Gardin
Daniel J Campbell的其他文献
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{{ truncateString('Daniel J Campbell', 18)}}的其他基金
Control of CD8+ T cell migration and activation by Flightless-1
Flightless-1 控制 CD8 T 细胞迁移和激活
- 批准号:
10155177 - 财政年份:2021
- 资助金额:
$ 64.57万 - 项目类别:
Mechanisms of autoimmune disease risk in IL2/IL2RA-dependent immune tolerance
IL2/IL2RA依赖性免疫耐受中自身免疫性疾病风险的机制
- 批准号:
10358624 - 财政年份:2021
- 资助金额:
$ 64.57万 - 项目类别:
Control of CD8+ T cell migration and activation by Flightless-1
Flightless-1 控制 CD8 T 细胞迁移和激活
- 批准号:
10366045 - 财政年份:2021
- 资助金额:
$ 64.57万 - 项目类别:
Mechanisms of autoimmune disease risk in IL2/IL2RA-dependent immune tolerance
IL2/IL2RA依赖性免疫耐受中自身免疫性疾病风险的机制
- 批准号:
10553203 - 财政年份:2021
- 资助金额:
$ 64.57万 - 项目类别:
Regulation of cutaneous immunity and tissue-repair by a specialized population of CD4+ T cells
特殊 CD4 T 细胞群对皮肤免疫和组织修复的调节
- 批准号:
9384627 - 财政年份:2017
- 资助金额:
$ 64.57万 - 项目类别:
Regulation of cutaneous immunity and tissue-repair by a specialized population of CD4+ T cells
特殊 CD4 T 细胞群对皮肤免疫和组织修复的调节
- 批准号:
9926223 - 财政年份:2017
- 资助金额:
$ 64.57万 - 项目类别:
Targeting the IL-2/regulatory T cell axis for autoimmune disease prevention in realistic animal models
靶向 IL-2/调节性 T 细胞轴在真实动物模型中预防自身免疫性疾病
- 批准号:
10307124 - 财政年份:2017
- 资助金额:
$ 64.57万 - 项目类别:
Targeting the IL-2/regulatory T cell axis for autoimmune disease prevention in realistic animal models
靶向 IL-2/调节性 T 细胞轴在真实动物模型中预防自身免疫性疾病
- 批准号:
10062808 - 财政年份:2017
- 资助金额:
$ 64.57万 - 项目类别:
Control of CD8+ T cell activation and differentiation by the signaling adaptor BCAP
信号适配器 BCAP 控制 CD8 T 细胞活化和分化
- 批准号:
9177685 - 财政年份:2016
- 资助金额:
$ 64.57万 - 项目类别:
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