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.

摘要 费立光博士是西北大学过敏与免疫学系助理教授 费恩伯格大学医学院。她的临床和研究兴趣主要集中在嗜酸性粒细胞疾病上， 包括嗜酸性胃肠道疾病(EGID)、炎症性疾病 胃肠道组织中嗜酸性粒细胞的数量是由于Th2细胞对食物抗原的反应时间延长所致。 嗜酸性食管炎(EoE)和非食道EGID，如嗜酸性胃炎/十二指肠炎 (Eg/Eod)与严重的发病率有关，并对生活质量产生深远的负面影响。 如果不进行治疗，受影响的胃肠道节段会形成难以逆转的渐进性疤痕。 虽然嗜酸性粒细胞和特化的Th2细胞都与EGID的发病有关，但许多 他们的确切角色仍然存在疑问。此应用程序建议将重点放在 EGID中的嗜酸性粒细胞与无数其他嗜酸性粒细胞疾病的比较 过度嗜酸性粒细胞增多症。类似地，特化的Th2细胞被调用作为疾病的生物标志物 免疫球蛋白介导的疾病，如食物过敏和过敏性鼻结膜炎，这两种疾病有显著不同 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。 这个职业发展奖，在布鲁斯·博什内尔博士的指导下，专注于调查 EGID发病的细胞和分子机制。为了增进对这种疾病的认识 进程。光博士有初步证据表明，血液中有独特的嗜酸性粒细胞特征 在EGID中，它们与其他嗜酸性疾病中的血液嗜酸性粒细胞区分开来，而且专门的 EGID患者的循环Th2细胞不同于更传统的IgE介导的特应性条件下的Th2细胞， 这两种细胞类型的数量和质量的变化与治疗和疾病的反应密切相关 减刑。这一建议的中心假设是独特的血液中嗜酸性粒细胞和T淋巴细胞 签名将EGID定义为不同于其他嗜酸性疾病或食物的临床实体- 引发了疾病。这将通过3个互不重叠但互补的目标来解决：1)定义 EGID中独特的嗜酸性粒细胞特征，以区别于其他与嗜酸性粒细胞相关的 伴血嗜酸性粒细胞增多的疾病或特应性疾病；2)特化Th2细胞的准确鉴定 EGID与食物过敏的比较；3)评价饮食和类固醇治疗对血液的影响 EGID患者的嗜酸性粒细胞和特异性Th2淋巴细胞特征 这项创新的研究将使用邝其志博士产生的新数据来进一步研究EGID的区域 目前还知之甚少。重要的是，这一奖项将为匡威博士提供更多的职业生涯 发展和培训需要建立自己成功的研究团队，建立独立于 她的导师，并大大推进了她的事业研究EGID的发病机制。