# The regulation of early life interleukin-27 expression and metabolic impact

> **NIH NIH R03** · WEST VIRGINIA UNIVERSITY · 2020 · $76,000

## Abstract

PROJECT SUMMARY
Microbial infections are a major cause of infant mortality worldwide. For particularly vulnerable populations
such as pre-term and low birth weight babies, the risk of invasive infections further escalates. The neonatal
period is defined by a distinct or immature immune system, and many features of a protective host response to
infection are deficient as compared with older children and adults. Our laboratory has identified that expression
of the immune suppressive cytokine interleukin (IL)-27 is elevated in human and murine neonates. Other
recent studies have shown IL-27 to be a biomarker for early onset neonatal sepsis. This suggests that elevated
IL-27 may represent a risk factor and when further increased during bacterial challenge, compromise the host
immune response. We have shown that macrophages and myeloid-derived suppressor cells (MDSCs) are the
dominant sources of elevated IL-27 in the neonatal phase and their contributions manifest as elevated levels of
serum IL-27 compared with older populations. Cumulatively, this points to IL-27 as a host molecule that
represents a target for immune intervention to improve the host response and reduce susceptibility to infection
early in life. We present strong evidence in a mouse model that the absence of IL-27 signaling translates to
improved survival, better weight gain, and enhanced clearance of bacteria during neonatal sepsis. In the
current proposal, we seek to understand the regulation of elevated levels of early life IL-27 and the functional
consequence to neonates during infection. A deeper understanding of these aspects of IL-27 biology will help
to inform targeted approaches to mitigate IL-27-regulated deficiencies in the host response to infection. In the
first aim we explore the hypothesis that IL-27 genes are hypomethylated in neonates allowing for increased
expression that is reduced in adults by methylation. In the second aim we investigate the hypothesis that IL-27
contributes to the regulation of glucose homeostasis. This hypothesis is derived from the observation in our
murine sepsis model, that IL-27 receptor-deficient neonates resist hypoglycemia that develops during neonatal
sepsis. The transcriptome will be examined in tissues from wild-type and IL-27 receptor-deficient neonatal
pups in the presence and absence of infection. At the completion of this project, we expect to have an
enhanced understanding of regulatory mechanisms that contribute to differential IL-27 expression early in life
and uncovered a novel link between host immunity and glucose homeostasis. These findings will have
translational value and the potential to improve outcomes in human neonates.

## Key facts

- **NIH application ID:** 10040906
- **Project number:** 1R03AI154129-01
- **Recipient organization:** WEST VIRGINIA UNIVERSITY
- **Principal Investigator:** Cory Michael Robinson
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $76,000
- **Award type:** 1
- **Project period:** 2020-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10040906

## Citation

> US National Institutes of Health, RePORTER application 10040906, The regulation of early life interleukin-27 expression and metabolic impact (1R03AI154129-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10040906. Licensed CC0.

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