# Exploring the thymic origin of group 2 innate lymphoid cells

> **NIH NIH R56** · OKLAHOMA MEDICAL RESEARCH FOUNDATION · 2021 · $618,011

## Abstract

Abstract
Innate lymphoid cells (ILCs) play diverse roles in shaping innate and adaptive immunity. These cells exist as
heterogeneous populations and their identities are influenced by their tissue environments. Likewise, the
ontogeny of ILCs is also complex. Although ILCs are thought to arise from bone marrow progenitors or tissue
resident progenitors distributed during embryogenesis, work from our laboratory strongly suggest that ILCs at
least ILC2s can also be generated in the thymus, not only from multipotent progenitors but also from
committed T cell precursors. Our recent data using single cell RNA sequencing suggest that a substantial
fraction of the ILC-enriched population in the blood of wild type mice (WT) come from the thymus, and their
equivalents can also be found in peripheral tissues. We thus hypothesize that the thymus exports a
substantial amount of ILC precursors to the circulation, which may replenish ILC2s and/or other ILCs
in peripheral tissues in steady-state or upon immune challenges and the thymus-derived ILCs may
have distinct functions. In this renewal proposal, we intend to follow up on these new exciting findings and
determine the function of these thymus-derived ILC precursors and their biological significant. We will further
characterize thymus-derived ILC-precursors in the lung and small intestine and determine their frequencies
during mouse development. We will also identify thymus-derived ILC precursors in human blood, thus gaining
appreciation of the clinical relevance of these cells. We will then focus on learning the function of these
thymus-derived ILC precursors using in vitro and in vivo approaches, as well as adoptive transfer of purified
ILC precursors into Rag2-/-Il2g-/- mice which are devoid of ILCs. The behaviors of these cells in type 2 immune
reactions will be monitored. Finally, we will assess the cell-intrinsic functional differences among WT ILC2s
generated from bone marrow common lymphoid progenitors (CLP) and thymic DN1 and DN3 T cell precursors.
Taken together, studies outlined in this proposal will further our understanding of thymus-derived ILCs, which
will help establish a new paradigm regarding to the production and maintenance of ILC pools. Because the
presence of an active thymus represents one of the major differences between children and adults, knowledge
about thymus-derived ILCs may shed light on their different immune responses such as those during Covid-19
infection.

## Key facts

- **NIH application ID:** 10472249
- **Project number:** 2R56AI126851-06
- **Recipient organization:** OKLAHOMA MEDICAL RESEARCH FOUNDATION
- **Principal Investigator:** Xiao-Hong Sun
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $618,011
- **Award type:** 2
- **Project period:** 2016-06-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10472249

## Citation

> US National Institutes of Health, RePORTER application 10472249, Exploring the thymic origin of group 2 innate lymphoid cells (2R56AI126851-06). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10472249. Licensed CC0.

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