# Functions for novel IL-15-responsive macrophages in the uterus during pregnancy

> **NIH NIH K08** · CHILDREN'S HOSP OF PHILADELPHIA · 2021 · $185,328

## Abstract

PROJECT SUMMARY
The overall goal of this five-year proposal for a Mentored Clinical Scientist Research Career Development Award
is for me to develop into a productive, independent academic investigator in the field of reproductive immunology.
I completed an MD and a PhD in the field of basic cellular immunology, and I now seek to apply my interest in
dysregulated immunity to the public health threat of adverse fetal and maternal outcomes of pregnancy. I
graduated from the American Board of Pediatrics Accelerated Research Pathway for Residency in General, and
I completed my Fellowship in Neonatal-Perinatal Medicine at Children’s Hospital of Philadelphia (CHOP) and
the University of Pennsylvania (Penn). I joined the faculty of CHOP and Penn as an Attending Physician and
Instructor in the Division of Neonatology. My mentor for this award, Dr. Edward M. Behrens, is a physician-
scientist with a longstanding track record of scientific innovation and providing exceptional training to mentees
at all levels. As an internationally-recognized expert in innate immunity and inflammatory disorders, Dr.
Behrens’s work complements my own, and we are thus poised for productivity. My scientific advisory committee
includes scientists and physician-scientists with collective expertise in all aspects of the proposed work, from
placental biology to next-generation sequencing. I am also extremely fortunate to have the unreserved support
of CHOP and Penn, whose combined resources are unmatched.
Scientifically, this proposal focuses on roles for novel macrophages that I discovered under the guidance of Dr.
Behrens, called CD122+Macs, in normal and threatened pregnancy. Enriched in the uterus in mice and humans,
CD122+Macs express high levels of CD122, the hallmark of responsiveness to interleukin-15 (IL-15). These
novel Macs signal and function when exposed to IL-15, surprising because killer lymphocytes like natural killer
(NK) cells, not Macs, are the classical targets of IL-15. Disrupted homeostasis of IL-15 is associated with
numerous adverse outcomes of pregnancy, including preeclampsia and abnormal feto-placental growth but
through unknown mechanisms. Based on prior literature and my preliminary data, my central hypothesis is: IL-
15 exerts its influence over outcomes of pregnancy not only by maintaining NK cells but also by modulating the
inflammatory properties of novel CD122+Macs. The aims of this proposal will establish: 1) Mechanisms by which
CD122+Macs respond biochemically and transcriptionally to IL-15 and 2) IL-15-dependent requirements for
CD122+Macs in pregnancy in vivo. This proposal will close major gaps in knowledge regarding the mechanism
by which IL-15 acts on a novel cellular target to ensure maternal and fetal health during pregnancy. In
accordance with my career development objective to become a field leader in reproductive immunology, my
scientific proposal complements my current proficiency in cellular immunologic methods with training in
adva...

## Key facts

- **NIH application ID:** 10126432
- **Project number:** 1K08AI151265-01A1
- **Recipient organization:** CHILDREN'S HOSP OF PHILADELPHIA
- **Principal Investigator:** Scott Michael Gordon
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $185,328
- **Award type:** 1
- **Project period:** 2020-12-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10126432

## Citation

> US National Institutes of Health, RePORTER application 10126432, Functions for novel IL-15-responsive macrophages in the uterus during pregnancy (1K08AI151265-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10126432. Licensed CC0.

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