# Exploiting Novel Human Hemato-Lymphoid System Mice to Characterize the Ontogeny of Circulatory and Tissue-Resident Human NK cells

> **NIH NIH R21** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $234,000

## Abstract

ABSTRACT
The study of human infant immunity has been challenging due to the transient nature of this phase of life, the
ethical consideration, and the limited accessibility to critical sites of immune cell development beyond the
umbilical and peripheral blood source. One approach for studying the human immune system in vivo is the use
of humanized mice. However, while the conventional models (e.g., NSG mice) allow an efficient development
of human T and B cells, these models failed to support the development of human NK cells. As a result,
exploring human NK cell development and function in vivo remained largely disadvantaged until the recent
technological development of human hemato-lymphoid system mice in which the genes of human cytokines
were knocked into their respective mouse loci, allowing for a successful development of human NK cells. In
this capacity, these human hemato-lymphoid system mice represent the best mouse model currently available
to permit the study of human NK cells in vivo. The premise of this proposal is to establish, using these system
mice, an animal model for the study of human NK cell ontogeny that could be used for validation and targeted
immunotherapies in pediatric diseases. Specifically, the goal of this proposal is to characterize the ontogeny of
circulatory and tissue-resident human NK cells (Aim 1), and trace the age-dependent changes of TGFβR
pathway during the maturation of human NK cells from early to adult life (Aim 2). At completion of Aim 1, we
expect to obtain a map to trace the dynamic and distribution of human precursor NK cells, conventional
circulatory NK cells, and tissue-resident NK cells. Currently, there is no available information on genomic
profiling of human NK cells during ontogeny, which underscores the value of the data to be generated under
Aim 2.

## Key facts

- **NIH application ID:** 9944446
- **Project number:** 5R21AI140106-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Yasmina Laouar
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $234,000
- **Award type:** 5
- **Project period:** 2019-06-06 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9944446

## Citation

> US National Institutes of Health, RePORTER application 9944446, Exploiting Novel Human Hemato-Lymphoid System Mice to Characterize the Ontogeny of Circulatory and Tissue-Resident Human NK cells (5R21AI140106-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9944446. Licensed CC0.

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