# A myeloid sentinel that secretes leukotrienes to activate type 2 immunity

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2022 · $264,750

## Abstract

Project Summary/Abstract
Sensing is the obligate first step of any immune response, resulting in activation of early innate signals that
direct subsequent adaptive immunity. The sensing of bacteria, viruses, and fungi has been defined in detail,
but our understanding of how parasitic worms (helminths) and allergens are detected to initiate “type 2”
immunity remains lacking. Group 2 innate lymphoid cells (ILC2s) are among the first immune cells activated in
a type 2 response, but they do not directly sense foreign agonists. Instead, host-derived signals from the
surrounding tissues activate ILC2s. One such signal is cysteinyl leukotrienes (cysLT), which are required to
activate both intestinal and airway ILC2s. Over time, ILC2s are replaced by effector and memory Th2 cells that
acquire an ILC2-like transcriptional and epigenetic phenotype. These Th2 cells can be activated by IL-33 in the
absence of antigen, but a role for cysLT in driving this innate-like function has not been tested. In the intestine,
cysLTs must be produced by epithelial tuft cells, but tuft cells are largely dispensable for airway type 2
inflammation. In Aim 1 of this proposal, we seek to identify the cellular source of cysLTs that activate airway
ILC2s during helminth infection. In Aim 2, we test the cell intrinsic role of cysLT signaling in Th2 effector and
memory cells. Our studies promise to reveal tissue-specific paradigms for initiation and maintenance of type 2
immunity, thereby suggesting new strategies for therapeutic intervention.

## Key facts

- **NIH application ID:** 10507701
- **Project number:** 1R21AI171159-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Jakob H. von Moltke
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $264,750
- **Award type:** 1
- **Project period:** 2022-07-05 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10507701

## Citation

> US National Institutes of Health, RePORTER application 10507701, A myeloid sentinel that secretes leukotrienes to activate type 2 immunity (1R21AI171159-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10507701. Licensed CC0.

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