# Peripheral Immune Development in Premature Infants with  and without NEC

> **NIH NIH R21** · YALE UNIVERSITY · 2021 · $232,498

## Abstract

Title:
Peripheral Immune Development in Premature Infants with and without NEC
Abstract:
Necrotizing enterocolitis (NEC) is a devastating complication of prematurity that frequently results in death (20-
50%) or severe systemic complications. Although NEC is a multifactorial disease, its precise etiology continues
to be poorly understood. As such, there are still no effective prevention methods or treatments available. Given
increased intestinal and systemic inflammation seen in NEC, it is likely that the dysregulation of the immune
system contributes to its pathogenesis. In order to better understand NEC pathogenesis, it is essential to have
a solid understanding of normal immune development that occurs over the first two months of age in premature
infants. Our preliminary data obtained from fetuses, patients with NEC and control subjects, show that there is a
drastic reduction of total and tissue resident memory T cells in the intestinal tissue and an increase in T cells in
the periphery. Moreover, NEC is associated with a significant increase in pro-inflammatory macrophages in
intestinal tissue, and a concomitant decrease in circulating monocytes. Recent work has begun to address how
neonatal peripheral immunity develops. However, data on the peripheral immune development in premature
infants over the first two months of life is sparse. Therefore, the goal of this exploratory proposal is to define
normal immune development of premature infants over the first two months of life and characterize its
dysregulation in patients with NEC. The overarching hypothesis of this proposal is that development of the
peripheral immune system in preterm infants is different in the innate and adaptive immune
compartments from that of term infants, and it is this difference that makes them susceptible to NEC. As
the blood volume in premature infants is limited, we have developed a methodology to perform deep
immunophenotyping on as little as 100 µliters of blood using mass cytometry time of flight (CyTOF). This unique
methodology will allow us to address the hypothesis, with the following aims: 1) Define the peripheral immune
development of premature infants (<32 weeks) over the first two months of life. We will perform CyTOF on
peripheral blood from 50 premature infants, with samples collected at 0, 1, 2, 4, and 8 weeks. Deep
characterization of the immune cell landscape and maps of the developmental trajectories of the major cell
lineages in premature infants will be generated. 2) Identify peripheral immune cell abnormalities associated
with the development of NEC. We will identify dysregulation of immune population trajectories specific to
premature infants who develop NEC. This information will provide us with a model for the immune cell
mechanism underlying susceptibility to NEC. This project would represent the first detailed deep examination of
the development of the immune system in premature infants with and without NEC over the first two months,
and w...

## Key facts

- **NIH application ID:** 10229527
- **Project number:** 5R21HD102565-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Liza Konnikova
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $232,498
- **Award type:** 5
- **Project period:** 2020-08-05 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10229527

## Citation

> US National Institutes of Health, RePORTER application 10229527, Peripheral Immune Development in Premature Infants with  and without NEC (5R21HD102565-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10229527. Licensed CC0.

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