Deciphering the roles of eosinophils and T lymphocytes in EGID
NIH
NORTHWESTERN UNIVERSITY AT CHICAGO
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. NARRATIVE Eosinophilic gastrointestinal diseases (EGIDs) of the upper GI tract are predominantly food-triggered chronic eosinophilic disorders with significant impact on quality of life and predictive, non-invasive diagnostic testing and treatments are sorely lacking. This proposal aims to expand and deepen our knowledge of two types of immune cells, namely eosinophils and specialized T cells, in EGID pathogenesis in a cohort of well- characterized EGID patients. The knowledge gained will ultimately impact patient care by improving diagnostics, providing biomarkers for monitoring disease activity and identifying potential targets for novel therapeutics.
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