# Understanding diet-microbiota interactions in small intestine eosinophil tissue residency during homeostasis and eosinophilic granulomatosis with polyangiitis (EGPA)

> **NIH NIH K08** · YALE UNIVERSITY · 2024 · $173,556

## Abstract

PROJECT SUMMARY/ABSTRACT
 This proposal describes a rigorous five-year training program leading to the career development of Dr.
Lisa L. Korn as an independent physician scientist. The principal investigator is a physician scientist with a PhD
in immunology who recently completed clinical fellowship training in rheumatology. Her career goal is to become
an independent investigator working at the intersection of mucosal immunology and inflammatory diseases,
studying how environmental influences in inflammatory disease are mediated by the intestinal immune system.
She proposes to expand her training in gut physiology, the microbiome, and inflammation biology through an
intensive training research experience under the mentorship of Dr. Ruslan Medzhitov, a pioneer and world leader
in the complex biology of inflammation. In addition to intellectual mentoring and hands-on training in Dr.
Medzhitov’s lab, she has designed a series of relevant didactic coursework and has carefully selected an
advisory committee with extensive expertise both related to this project and in successfully mentoring physician-
scientists. An outstanding scientific environment and extensive resources are provided by Yale University and
its Departments of Medicine, Immunobiology, and section of Rheumatology.
 The research objective of this proposal is to study the interactions between nutrient signals and
microbiota on eosinophil residency in the small intestine at steady state and in a mouse model of eosinophilic
granulomatosis with polyangiitis (EGPA), an eosinophilic vasculitis that often involves the intestine. We found
that small intestine eosinophils undergo a process of tissue adaption at steady state that involved transit of
eosinophils up the crypt-villus axis with time, and changes in eosinophil morphology, surface marker expression,
and transcriptional profile. The canonical eosinophil survival factor IL-5 was largely dispensable for eosinophil
adaptation, while the vitamin A metabolite retinoic acid was required. Because small intestine eosinophils are
most abundant in the part of the intestine that is most exposed to luminal nutrients, we asked whether these cells
were further regulated by diet. Indeed, a high protein diet caused depletion of the villus-resident subset. Based
on these findings, we hypothesize that coordinated environmentally derived signals regulate eosinophil small
intestine tissue adaptation, and that they might affect intestinal eosinophilia in EGPA. Therefore, we propose to
identify how retinoic acid and dietary protein impact the eosinophil small intestine adaptation process, to
determine the impact of the localization of the intestinal microbiota on this process, and to identify mechanisms
of intestinal eosinophilia in a mouse model of EGPA.

## Key facts

- **NIH application ID:** 10865312
- **Project number:** 1K08AR084069-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Lisa Lenore Korn
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $173,556
- **Award type:** 1
- **Project period:** 2024-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10865312

## Citation

> US National Institutes of Health, RePORTER application 10865312, Understanding diet-microbiota interactions in small intestine eosinophil tissue residency during homeostasis and eosinophilic granulomatosis with polyangiitis (EGPA) (1K08AR084069-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10865312. Licensed CC0.

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