Deciphering the roles of eosinophils and T lymphocytes in EGID
解读嗜酸性粒细胞和 T 淋巴细胞在 EGID 中的作用
基本信息
- 批准号:10663530
- 负责人:
- 金额:$ 19.1万
- 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:2023-02-01 至 2028-01-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAdrenal Cortex HormonesAffectAllergicAllergic DiseaseAreaAutomobile DrivingAwardBiological MarkersBiological ProductsBloodCareer MobilityCaringCell surfaceCellsCharacteristicsChronicCicatrixClinicalClinical ResearchDataDedicationsDeglutitionDiagnosisDiagnosticDiagnostic testsDietDiseaseDisease remissionDisparateDisseminated eosinophilic collagen diseaseElemental DietsEosinophiliaEosinophilic EsophagitisEosinophilic GastritisEosinophilic Gastrointestinal DiseaseEsophagusEvaluationFlow CytometryFoodFood HypersensitivityGastrointestinal DiseasesGastrointestinal tract structureGenesHumanHypersensitivityIL17 geneIL5 geneIgEImmuneImmune responseImmunologyImmunophenotypingInflammationInflammatoryInterferon Type IIInterleukin-13Interleukin-5K-Series Research Career ProgramsKnowledgeLymphocyteMediatingMentored Patient-Oriented Research Career Development AwardMentorsMentorshipMethodsMolecularMonitorMorbidity - disease rateOutcome MeasurePathogenesisPathogenicityPathway interactionsPatient CarePatient Outcomes AssessmentsPatientsPhysiciansPlayProcessProductionPublishingQuality of lifeRNARNA purificationResearchResolutionRoleSamplingScientistSpecificitySteroidsSymptomsT-LymphocyteT-cell receptor repertoireTechnologyTestingTh2 CellsTissue-Specific Gene ExpressionTissuesTrainingTranscriptUniversitiesUpper digestive tract structurecareer developmentcell typecohortcytokinedietaryduodenitisenvironmental allergyeosinophileosinophilic asthmaeosinophilic inflammationfood antigenimprovedinnovationinterestmedical schoolsmemory CD4 T lymphocytenew therapeutic targetnoninvasive diagnosisnovelprofessorrecruitresponserhinoconjunctivitissingle-cell RNA sequencingtranscriptome sequencingtreatment effecttreatment response
项目摘要
ABSTRACT
Dr. Fei Li Kuang is an Assistant Professor in the Division of Allergy and Immunology at Northwestern
University Feinberg School of Medicine. Her clinical and research interests focus on eosinophilic disorders,
including eosinophilic gastrointestinal disorders (EGIDs), inflammatory diseases defined by excessive
numbers of GI tissue eosinophils as result of an inappropriate prolonged Th2 response to food antigens.
Both eosinophilic esophagitis (EoE) and non-esophageal EGIDs such as eosinophilic gastritis/duodenitis
(EG/EoD) are associated with significant morbidity and have a profoundly negative impact on quality of life.
When untreated, there is progressive scarring of the affected GI tract segments that is not easily reversible.
While both eosinophils and specialized Th2 cells are implicated in EGID pathogenesis, numerous
questions remain as to their precise roles. This application proposes to focus on what is different about
eosinophils in EGID as compared to myriad number of other eosinophilic disorders accompanied by
excessive blood eosinophilia. Similarly, specialized Th2 cells are invoked to be biomarkers of disease in
IgE-mediated disorders such as food allergy and allergic rhino-conjunctivitis, which are markedly different
allergic diseases from EGID, so what makes these cells different in EGID will also be examined.
This career development award, under the mentorship of Dr. Bruce Bochner, focuses on investigating the
cellular and molecular mechanisms of EGID pathogenesis. to advance the understanding of this disease
process. Dr. Kuang has preliminary evidence suggesting that there are unique blood eosinophil signatures
in EGIDs that distinguish them from blood eosinophils in other eosinophilic disorders, and that specialized
circulating Th2 cells in EGIDs differ from those identified in more traditional IgE-mediated atopic conditions,
and that quantitative and qualitative changes in both cell types track with response to therapy and disease
remission. The central hypothesis of this proposal is that unique blood eosinophil and T lymphocyte
signatures define EGID as a clinical entity distinct from other eosinophilic disorders or food-
triggered diseases. This will be addressed by 3 non-overlapping but complementary aims: 1) Definition
of unique blood eosinophil signatures in EGID that distinguish it from other eosinophil-associated
disorders or atopic disorders with blood eosinophilia; 2) Precise identification of the specialized Th2 cells
in EGID as compared to food allergy; 3) Evaluation of the effect of dietary and steroid treatment on blood
eosinophil and specialized Th2 lymphocyte signatures in EGID
This innovative study will use novel data generated by Dr. Kuang to further investigate areas of EGID that
are currently poorly understood. Importantly, this award will provide Dr. Kuang with additional career
development and training needed to build her own successful research team, establish independence from
her mentor and significantly advance her career studying EGID pathogenesis.
摘要
博士Fei Li Kuang是西北大学过敏和免疫学系的助理教授
范伯格大学医学院。她的临床和研究兴趣集中在嗜酸性粒细胞疾病,
包括嗜酸性胃肠疾病(EGID)、由过度炎症引起的炎性疾病、
胃肠道组织嗜酸性粒细胞的数量,作为结果的不适当的延长Th 2反应的食物抗原。
嗜酸性粒细胞性食管炎(EoE)和非食管EGID,如嗜酸性粒细胞性胃炎/胃炎
(EG/EoD)与显著的发病率相关,并对生活质量产生深远的负面影响。
如果不治疗,受影响的胃肠道节段会出现进行性瘢痕形成,这是不容易逆转的。
虽然嗜酸性粒细胞和特化Th 2细胞都参与EGID发病机制,但许多
至于它们的确切作用,仍有疑问。此应用程序建议重点关注
EGID中的嗜酸性粒细胞与无数其他伴有
血嗜酸性粒细胞过多。类似地,特化的Th 2细胞被援引为疾病的生物标志物,
IgE介导的疾病,如食物过敏和过敏性鼻结膜炎,
过敏性疾病,所以什么使这些细胞在EGID不同也将被检查。
在布鲁斯·博什纳博士的指导下,这个职业发展奖专注于调查
EGID发病机制的细胞和分子机制。来增进对这种疾病的了解
过程匡医生有初步证据表明,有独特的血液嗜酸性粒细胞签名
在EGID中,将其与其他嗜酸性粒细胞疾病中的血液嗜酸性粒细胞区分开来,
EGID中的循环Th 2细胞不同于在更传统的IgE介导的特应性病症中鉴定的那些,
并且这两种细胞类型的数量和质量变化都与对治疗和疾病的反应有关
缓解。这一建议的中心假设是,独特的血液嗜酸性粒细胞和T淋巴细胞
特征将EGID定义为不同于其他嗜酸性粒细胞性疾病或食物-
引发的疾病。这将通过三个不重叠但互补的目标来解决:1)定义
EGID中独特的血液嗜酸性粒细胞特征将其与其他嗜酸性粒细胞相关的
具有血液嗜酸性粒细胞增多症的疾病或特应性疾病; 2)精确鉴定特化的Th 2细胞
3)评价饮食和类固醇治疗对血液中的蛋白质的影响;
EGID中的嗜酸性粒细胞和特化Th 2淋巴细胞特征
这项创新研究将使用Kuang博士生成的新数据进一步研究EGID的领域,
目前还知之甚少。重要的是,这个奖项将为邝博士提供额外的职业生涯
发展和培训需要建立自己的成功的研究团队,建立独立,
她的导师,并显着推进她的职业生涯研究EGID发病机制。
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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Fei Li Kuang其他文献
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