# Relationship between the ontogeny of immunosuppression and increased susceptibility to infection during infancy

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

## Abstract

ABSTRACT
Immaturity of the immune system in neonates and infants represents an underlying factor for increased
susceptibility to infection that threaten childhood. However, the exact mechanisms responsible for immaturity of
the immune system remain to date uncharacterized. Work from my laboratory provided evidence that
immaturity of Natural Killer (NK) cells is orchestrated by TGFβ. We demonstrated that NK cells are able to
complete maturation early in life if TGFβR signaling is blocked. A point of crucial consequence of this
advantage is efficient control of cytomegalovirus infection in infant mice with NK cells lacking TGFβR signaling.
The overall goal of this proposal is to elucidate the cellular and molecular mechanisms by which TGFβ
imposes constraints on NK cell immune maturation during infancy and to identify the factors upstream and
downstream of TGFβR signaling that dictate the fate of infant NK cell immaturity. Three specific aims will be
addressed in this proposal: (1) define the make-up of TGFβ signaling pathway in infant NK cells, (2) determine
whether hematopoiesis in early life is conducive to higher availability/activity of TGFβ, and (3) establish the
relationship between the prevalence of neonatal suppressor cells and immaturity of NK cells during infancy.
The continuing high global burden of infections in children elucidates the need for on-going basic and
translational studies in the area of neonatal and infant immune ontogeny. Distinct early life immune ontogeny
will certainly have direct implications for current and future pediatric therapies. In that regard, this project holds
substantial promise in unraveling new strategies that can be applied to unlock the NK cell deficit in early life, a
deficit that was originally thought intangible.

## Key facts

- **NIH application ID:** 9842397
- **Project number:** 5R21AI138180-02
- **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:** 2019-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9842397

## Citation

> US National Institutes of Health, RePORTER application 9842397, Relationship between the ontogeny of immunosuppression and increased susceptibility to infection during infancy (5R21AI138180-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9842397. Licensed CC0.

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