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：
Fei Li Kuang
金额：
$ 19.1万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
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：
https://reporter.nih.gov/project-details/10663530
关键词：
Address Adrenal Cortex Hormones Affect Allergic Allergic Disease Area Automobile Driving Award Biological Markers Biological Products Blood Career Mobility Caring Cell surface Cells Characteristics Chronic Cicatrix Clinical Clinical Research Data Dedications Deglutition Diagnosis Diagnostic Diagnostic tests Diet Disease Disease remission Disparate Disseminated eosinophilic collagen disease Elemental Diets Eosinophilia Eosinophilic Esophagitis Eosinophilic Gastritis Eosinophilic Gastrointestinal Disease Esophagus Evaluation Flow Cytometry Food Food Hypersensitivity Gastrointestinal Diseases Gastrointestinal tract structure Genes Human Hypersensitivity IL17 gene IL5 gene IgE Immune Immune response Immunology Immunophenotyping Inflammation Inflammatory Interferon Type II Interleukin-13 Interleukin-5 K-Series Research Career Programs Knowledge Lymphocyte Mediating Mentored Patient-Oriented Research Career Development Award Mentors Mentorship Methods Molecular Monitor Morbidity - disease rate Outcome Measure Pathogenesis Pathogenicity Pathway interactions Patient Care Patient Outcomes Assessments Patients Physicians Play Process Production Publishing Quality of life RNA RNA purification Research Resolution Role Sampling Scientist Specificity Steroids Symptoms T-Lymphocyte T-cell receptor repertoire Technology Testing Th2 Cells Tissue-Specific Gene Expression Tissues Training Transcript Universities Upper digestive tract structure career development cell type cohort cytokine dietary duodenitis environmental allergy eosinophil eosinophilic asthma eosinophilic inflammation food antigen improved innovation interest medical schools memory CD4 T lymphocyte new therapeutic target noninvasive diagnosis novel professor recruit response rhinoconjunctivitis single-cell RNA sequencing transcriptome sequencing treatment effect treatment response

Address Adrenal Cortex Hormones Affect Allergic Allergic Disease Area Automobile Driving Award Biological Markers Biological Products Blood Career Mobility Caring Cell surface Cells Characteristics Chronic Cicatrix Clinical Clinical Research Data Dedications Deglutition Diagnosis Diagnostic Diagnostic tests Diet Disease Disease remission Disparate Disseminated eosinophilic collagen disease Elemental Diets Eosinophilia Eosinophilic Esophagitis Eosinophilic Gastritis Eosinophilic Gastrointestinal Disease Esophagus Evaluation Flow Cytometry Food Food Hypersensitivity Gastrointestinal Diseases Gastrointestinal tract structure Genes Human Hypersensitivity IL17 gene IL5 gene IgE Immune Immune response Immunology Immunophenotyping Inflammation Inflammatory Interferon Type II Interleukin-13 Interleukin-5 K-Series Research Career Programs Knowledge Lymphocyte Mediating Mentored Patient-Oriented Research Career Development Award Mentors Mentorship Methods Molecular Monitor Morbidity - disease rate Outcome Measure Pathogenesis Pathogenicity Pathway interactions Patient Care Patient Outcomes Assessments Patients Physicians Play Process Production Publishing Quality of life RNA RNA purification Research Resolution Role Sampling Scientist Specificity Steroids Symptoms T-Lymphocyte T-cell receptor repertoire Technology Testing Th2 Cells Tissue-Specific Gene Expression Tissues Training Transcript Universities Upper digestive tract structure career development cell type cohort cytokine dietary duodenitis environmental allergy eosinophil eosinophilic asthma eosinophilic inflammation food antigen improved innovation interest medical schools memory CD4 T lymphocyte new therapeutic target noninvasive diagnosis novel professor recruit response rhinoconjunctivitis single-cell RNA sequencing transcriptome sequencing treatment effect treatment response

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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.

抽象的 Fei Li Kuang博士是西北地区过敏和免疫学系的助理教授大学费恩伯格医学院。她的临床和研究兴趣专注于嗜酸性疾病，包括嗜酸性胃肠道疾病（EGID），由过度定义的炎症性疾病由于对食品抗原的长时间反应，胃肠道嗜酸性粒细胞的数量是由于不适当的。嗜酸性食管炎（EOE）和非食道食管，例如嗜酸性胃炎/十二指肠炎（例如/EOD）与明显的发病率有关，并对生活质量产生深远的负面影响。如果不进行治疗，就会有受影响的胃肠道段的渐进性疤痕不易可逆。虽然嗜酸性粒细胞和专业的Th2细胞都与egid发病机理有关，但许多关于它们的确切角色仍然存在问题。本申请建议专注于不同的与无数其他嗜酸性疾病相比血液嗜酸性粒细胞增多。同样，专门的TH2细胞被引用为疾病的生物标志物 IgE介导的疾病，例如食物过敏和过敏性犀牛 - 连接性炎，它们明显不同 EGID的过敏性疾病，因此还将检查这些细胞在EGID中的不同之处。在布鲁斯·博切纳（Bruce Bochner）博士的指导下，该职业发展奖的重点是调查 EGID发病机理的细胞和分子机制。促进对这种疾病的理解过程。 Kuang博士有初步证据表明存在独特的血液嗜酸性标志在将它们与其他嗜酸性疾病中的血液嗜酸性粒细胞区分开的egid中 EGID中的循环Th2细胞与在更传统的IgE介导的特征条件下鉴定的细胞不同，以及两种细胞类型的定量和质量变化，都可以反应治疗和疾病缓解。该提议的中心假设是独特的血嗜酸性粒细胞和T淋巴细胞特征将EGID定义为与其他嗜酸性疾病或食物不同的临床实体触发疾病。这将通过3个非重叠但互补目的来解决：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血液嗜酸性粒细胞的疾病或特应性疾病； 2）精确鉴定专业的TH2细胞与食物过敏相比，在Egid中； 3）评估饮食和类固醇治疗对血液的影响 Egid中的嗜酸性粒细胞和专门的Th2淋巴细胞特征这项创新的研究将使用Kuang博士生成的新数据来进一步研究Egid的领域目前了解不足。重要的是，该奖项将为Kuang博士提供其他职业建立自己成功的研究团队所需的发展和培训，建立独立于她的导师并大大提高了她研究埃奇发病机理的职业。