# Maternal Microbial Influences on Early-life Thymic T cell development

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $504,000

## Abstract

PI/PD: Jain, Nitya Ph.D.
PROJECT SUMMARY
The mammalian fetus develops in a relatively sterile fetal environment in utero. In humans, precursor cells
seed the fetal thymus at gestational week (GSW) 9-10 and ‘single-positive’ T cells begin to arise and populate
lymphoid organs by GSW15. Multiple other lineages of immune cells including innate and innate-like gd T cells,
invariant Natural Killer T (iNKT) cells, Mucosal Associated Invariant T (MAIT) cells and Innate Lymphoid cells
(ILCs) are also found in the thymus and develop in a complex process that is temporally regulated. At birth, the
still developing immune system of the newborn is exposed to a multitude of environmental antigens including
the burgeoning intestinal microbiota. Microbial colonization during the first days and weeks after birth has
profound effects on immune system development. However, recent studies have highlighted the contribution of
maternal microbes in guiding intestinal immune cell homeostasis in their offspring during gestation. Whether
maternal microbes also influence fetal and postnatal thymic immune cell development and function is
not known.
Our long-term goal is to understand how microbes and microbial mediators impact early-life immune system
development and function. The specific objective of this proposal is to identify and characterize maternal
microbial influence of developing thymic cells in progeny. Based on our preliminary data, we hypothesize that
maternal microbes and maternal TLR2 signals direct the development and functional maturation of
thymic PLZF-expressing immune cells in offspring. We will test this hypothesis in the experiments of the
following Aims. Aim 1: Determine the role of maternal microbes in influencing offspring thymic lymphocyte
development. Aim 2: Dissect the role of maternally expressed TLR2 on offspring thymic lymphocyte
development. Our studies will provide deeper insight into an early life immune developmental process that will
reveal new strategies to target maternal microbes to promote fetal and infant health. These studies will also
advance our understanding of maternal-fetal communications in the context of pregnancy-related infections
and their impact on offspring immune health.

## Key facts

- **NIH application ID:** 10065870
- **Project number:** 1R01AI154626-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Nitya Jain
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $504,000
- **Award type:** 1
- **Project period:** 2020-06-12 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10065870

## Citation

> US National Institutes of Health, RePORTER application 10065870, Maternal Microbial Influences on Early-life Thymic T cell development (1R01AI154626-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10065870. Licensed CC0.

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