# Role of innate immune recognition in adaptive T cell development in early life

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $192,320

## Abstract

PI/PD: Jain, Nitya Ph.D.
PROJECT SUMMARY
The immune system of the newborn faces unique challenges in the period immediately following birth. Thrust
from a sterile fetal environment, it is abruptly exposed to an immense array of foreign antigens, the major
burden of which is in the form of the microbiota newly colonizing the gastrointestinal tract. Breakdown of
tolerance to intestinal microbiota precipitates autoimmunity in adults. Postnatal immunity, however, is largely
immature and relies primarily on innate immune effectors for protection against infection and autoimmunity.
Both adaptive and innate lymphocytes develop in the thymus. How do the needs of gut immunity get
transmitted to the thymus at this critical time in the development of the neonate? It is clear that gut microbiota
regulate the maturation of the immune system at mucosal sites. However, a central unresolved question
remains how intestinal microbial colonization influences immune cells development in the primary lymphoid
organ, the thymus.
The long-term goal of this study is to understand how the postnatal immune system develops in the presence
of the maturing intestinal microbiota that impacts immunity in adulthood. The specific objective of this proposal
is to explore the role of the Toll-like Receptor 2 (TLR2) pathway in mediating entero-thymic communication that
regulates the development of immune cell subsets in early life. We propose that TLR2-microbiota interactions
shape immune system development in early life. We hypothesize that these interactions impact thymic
development of specific immune cell subsets in early life. We will address this in the experiments of the
following Specific Aims. Specific Aim 1: Determine in which cell subset is TLR2 required to regulate thymic T
cell development. Specific Aim 2: Determine when during ontogeny is TLR2 required to regulate thymic T cell
development. Specific Aim 3: Determine the impact of TLR2-deficiency on entero-thymic communication.
Microbiota regulation of thymic development is a novel concept and has tremendous therapeutic potential,
especially in preterm infants that suffer from severe disorders stemming from immunological imbalances.
Strategies targeting microbiota and the host pathways they affect may provide benefits to a substantial number
of these preterm infants.

## Key facts

- **NIH application ID:** 9850930
- **Project number:** 5R21AI139735-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Nitya Jain
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $192,320
- **Award type:** 5
- **Project period:** 2019-01-16 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850930

## Citation

> US National Institutes of Health, RePORTER application 9850930, Role of innate immune recognition in adaptive T cell development in early life (5R21AI139735-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9850930. Licensed CC0.

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