# Myeloid derived IL-33 controls Treg responses during parasite infection

> **NIH NIH R01** · TULANE UNIVERSITY OF LOUISIANA · 2024 · $243,913

## Abstract

Project Summary
The interleukin 1 (IL-1) cytokine superfamily member IL-33 drives host protection against gastrointestinal (GI)
pathogens through mechanisms that remain unclear. Paradoxically, IL-33 responsiveness in different
lymphocyte subsets dictates its pro- vs. anti-inflammatory roles evinced by its ability to promote expansion of
group 2 innate lymphoid cells (ILC2) or Foxp3+ regulatory T cells (Tregs), respectively. Whether source of IL-33
influences its biological role has been largely ignored due the current paradigm that IL-33 is only released from
damaged structural cells (e.g. epithelial cell lineages). However, our recently published data show that intestinal
epithelial cell (IEC)-derived IL-33 drives ILC2 responses and GI helminth immunity, whereas dendritic cell (DC)-
derived IL-33 drives ST2+Foxp3+ Treg responses and helminth susceptibility. This proposal seeks to understand
the mechanisms responsible for IL-33 expression and production in the myeloid lineage and further investigates
whether IL-33 cellular context controls the balance between inflammation vs. immunosuppression during
protozoan infections as it does in helminth infections. Our project tests the central hypothesis that cellular
source of IL-33 determines whether IL-33 serves a protective or pathogenic role during GI parasite
infection through controlling intestinal Treg subset expansion. We will test this hypothesis in two specific
aims (SA). Experiments proposed in SA1 will: a) transcriptionally profile IL-33+ vs. IL-33- DC to determine whether
IL-33 expressing APC constitute a distinct subset, b) employ microscopy and imaging mass spectrometry to
understand the tissue niches where these cells reside, and c) determine whether DC-derived IL-33 is critical for
the maintenance and/or induction of distinct subsets of Foxp3+ Treg through microbial-dependent mechanisms.
SA2 will generate mice that allow IL-33 deletion in distinct DC-subsets and tissue macrophage populations to
determine their impact on intestinal tissue homeostasis and host protection against GI pathogens. Lastly, we will
determine whether epithelial vs. myeloid derived-IL-33 controls microbial dysbiosis and the pathological outcome
following oral Toxoplasma gondii infection. Taken together, this project seeks to expand the basic understanding
of how the cellular context of cytokine production impacts immunity against important human GI pathogens.

## Key facts

- **NIH application ID:** 11223557
- **Project number:** 7R01AI164715-05
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** De'Broski R Herbert
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $243,913
- **Award type:** 7
- **Project period:** 2021-08-06 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11223557

## Citation

> US National Institutes of Health, RePORTER application 11223557, Myeloid derived IL-33 controls Treg responses during parasite infection (7R01AI164715-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11223557. Licensed CC0.

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