Eosinophils have been considered end-stage cells involved in host protection against parasites. However, numerous lines of evidence have now changed this perspective by showing that eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of diverse inflammatory responses, as well as modulators of innate and adaptive immunity. For example, the Rothenberg laboratory has found that intestinal eosinophils regulate the production of secretory immunoglobulin A (IgA) and regulate intestinal commensal flora.
We are examining new views on the role of eosinophils in homeostatic function, including developmental biology and innate and adaptive immunity (as well as interaction with mast cells, B cells and T cells). We are studying the molecular steps involved in eosinophil development and trafficking, with special attention to the important role of eosinophil-selective cytokines such as interleukin 5 (IL-5), the eotaxin subfamily of chemokines, IL-13 and epithelial gene products.
We are investigating the role of eosinophils in disease processes including infections, asthma and gastrointestinal disorders. We are studying the consequences of genetically engineered eosinophil-deficient mice and eosinophil depletion in humans ("human eosinophil knockouts"). Genetic approaches to understanding eosinophil-associated human diseases are a focus area. Why patients develop allergic disorders, focused on genetic and environmental factors and their interactions, are priority research topics. Finally, we are pursuing strategies for diagnostics and patient-reported outcomes (e.g., PEESS v2.0) and targeted therapeutic intervention in allergic diseases with a focus on eosinophil-mediated diseases.
Epithelial cells are the first line of defense against foreign antigens. We are researching the role of epithelial cells as an innate immune organ. Studies focus on stem cell biology, differentiation and repair. Recent findings include the 1) role of anti-proteases in maintaining homeostasis (e.g., Science Translational Medicine 2020) and 2) identification and role of RipIL33, an allergen sensor that triggers IL-33 maturation and release (Nature Immunology 2021).
The Rothenberg CURED Research Lab is an active member of research, professional and patient advocacy communities for allergic and eosinophilic conditions. Learn more in our video library.
Marc E. Rothenberg, MD, PhD
Division of Allergy and Immunology
Read the Lancet: Gastroenterology and Hepatology In Focus Profile on Marc Rothenberg's career and contributions: Passionately Curious