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

• 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
• 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

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 费丽匡博士是西北大学过敏与免疫学系助理教授 大学范伯格医学院。她的临床和研究兴趣集中在嗜酸性粒细胞疾病、 包括嗜酸粒细胞性胃肠道疾病 (EGID)、嗜酸性粒细胞过多定义的炎症性疾病 由于对食物抗原的不适当的长期 Th2 反应，导致胃肠道组织嗜酸性粒细胞数量增加。 嗜酸性粒细胞性食管炎 (EoE) 和非食管 EGID，例如嗜酸性胃炎/十二指肠炎 (EG/EoD) 与显着的发病率相关，并对生活质量产生深远的负面影响。 如果不治疗，受影响的胃肠道部分会逐渐形成疤痕，且不易逆转。 虽然嗜酸性粒细胞和特化 Th2 细胞都与 EGID 发病机制有关，但许多 关于它们的确切作用仍然存在疑问。该应用程序建议重点关注以下内容的不同之处： EGID 中的嗜酸性粒细胞与无数其他伴有嗜酸性粒细胞疾病的疾病相比 血液嗜酸性粒细胞增多。同样，特化的 Th2 细胞被用作疾病的生物标志物。 IgE 介导的疾病，例如食物过敏和过敏性鼻结膜炎，两者明显不同 EGID 引起的过敏性疾病，因此也将检查这些细胞在 EGID 中的不同之处。 该职业发展奖在 Bruce Bochner 博士的指导下，重点调查 EGID发病机制的细胞和分子机制。加深对这种疾病的了解 过程。匡博士有初步证据表明存在独特的血液嗜酸性粒细胞特征 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，并且专门针对 EGID 中的循环 Th2 细胞与更传统的 IgE 介导的特应性疾病中所识别的细胞不同， 两种细胞类型的量和质的变化都与治疗和疾病的反应相一致 缓解。该提案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 定义为与其他嗜酸性粒细胞疾病或食物相关疾病不同的临床实体。 引发疾病。这将通过 3 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区别开来 伴有血液嗜酸性粒细胞增多的疾病或特应性疾病； 2) 精确识别特化的Th2细胞 EGID 与食物过敏相比； 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特化 Th2 淋巴细胞特征 这项创新研究将利用 Kuang 博士生成的新数据来进一步研究 EGID 的领域： 目前还知之甚少。重要的是，这个奖项将为匡博士提供额外的职业生涯 建立自己成功的研究团队所需的发展和培训，建立独立性 她的导师并极大地推进了她研究 EGID 发病机制的职业生涯。