# Migration and signaling in ILC2 in asthma:  Male and female differences

> **NIH VA IK2** · VA SALT LAKE CITY HEALTHCARE SYSTEM · 2021 · —

## Abstract

Project Summary: Candidate—The following application is intended to initiate the research career of Kristi J.
Warren, PhD within the VA Nebraska Western Iowa Health Care System under the mentorship of [Robert Paine
III, MD; a well-respected, VA-funded pulmonary researcher and clinician for the past 20+ years]. Dr. Warren
received her PhD in Immunobiology in 2012 and has since completed her postdoctoral training focused
exclusively in the pulmonary immunologic sciences. Environment—[The University of Utah is adjacent to the
George E. Wahlen VA Medical Center and research hospital where clinical and scientific relationships have been
established to complete the proposed studies.] The research environment is collegial and supportive with a
multitude of opportunities for interaction with other scientists with similar interests. Specifically, Dr. Warren will
have every opportunity to discuss/present her work for crucial feedback and direction from senior VA
researchers. Research—In recent years, asthma and other chronic respiratory illnesses are increasingly
diagnosed in the Veteran population. There is a sex-based disparity in asthma such that severe asthma is more
prevalent in adult female Veterans than males, and more asthma-linked deaths occur in women than men. In
general, ovarian hormones are thought to contribute to disease exacerbation, whereas testosterone protects
against asthma. Recently, attention was drawn to the group 2 innate lymphoid cells (ILC2), which are shown to
produce large amounts of asthma-promoting cytokines (IL-5 and IL-13) following allergen exposure. We
observed a sex difference in activated ILC2 such that lung ILC2 isolated from female allergen-treated mice
produced higher IL-5, IL-13, and the type 2 chemokines, CCL17 and CCL22, in comparison to males. In this
research proposal we will use gonadectomized female mice treated with slow-release hormone pellets to
evaluate the independent effect of estrogen, progesterone, and [testosterone] in experimental asthma. There
are two goals for Aim 1: (1) define sex differences in recruitment and localization of ILC2 in the lung mediated
through the chemokine receptors CCR4 and CRTH2 and their cognate chemokines, CCL17/22 and PGD2,
respectively (subaim 1a). (2) Subaim 1b will define the chemokine expression specifically by activated lung-ILC2
following allergen exposure. Because ILC2 are in close proximity to the airway epithelium and other resident
immune cells, these studies are designed to separate the sex hormone effect on the total chemokine milieu of
the lung from that of the activated ILC2. These studies will comprehensively define the sex hormone-based
effects on the chemokine milieu developed in the lung during allergen challenge. Aim 2 will investigate sex
differences in IL-33-mediated activation of ILC2, which drives the production of IL-5 and IL-13 through a MyD88-
dependent signaling pathway. IL-33-MyD88 signaling has not been previously evaluated in ILC2, nor has the
ef...

## Key facts

- **NIH application ID:** 10045501
- **Project number:** 5IK2BX004219-02
- **Recipient organization:** VA SALT LAKE CITY HEALTHCARE SYSTEM
- **Principal Investigator:** Kristi J Warren
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-10-01 → 2024-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10045501

## Citation

> US National Institutes of Health, RePORTER application 10045501, Migration and signaling in ILC2 in asthma:  Male and female differences (5IK2BX004219-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10045501. Licensed CC0.

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