# Placenta-specific miR-519c-mediated induction of immune tolerance in human placenta

> **NIH NIH R01** · NEW YORK UNIVERSITY D/B/A NYU LONG ISLAND SCHOOL OF MEDICINE · 2024 · $321,233

## Abstract

SUMMARY/ABSTRACT
 Pregnancy represents a unique challenge for the maternal-fetal immune interface, requiring the balance
between immunosuppression, essential for the maintenance of semi-allogeneic fetus and pro-inflammatory
host defense to protect the mother and fetus from invading organisms. Adaptation to repeated inflammatory
stimuli may be critical in preventing rejection of the fetus by the exaggerated maternal inflammatory responses
to mild/moderate infections that are common during human pregnancy.
 Immune tolerance/adaptation is a well-described phenomenon in which cells exposed to repeated
pathogens become less responsive to subsequent exposures. This adaptation suppresses an overly
aggressive inflammatory response to repeated infections that can be detrimental to the tissues rather than
protective. Dampened immune response to repeated infections has been associated with protection against
tissue injury and mortality in several human diseases. However, to date, the role of immune tolerance to
repeated infections in the context of human pregnancy, and the exact mechanisms that contribute to the
establishment of such immune adaptation to prevent inflammation-induced pathologic pregnancies are not
explored. There is now extensive evidence that miRNAs play an important role in the maintenance of a healthy
pregnancy, with a wide range of miRNAs implicated in endometrial receptivity, implantation, gestational tissues
function, and labor. Our preliminary results indicate that repeated LPS (gram negative bacterial toxins) or LTA
(gram-positive bacterial toxins) exposures to human placenta attenuates exaggerated inflammatory responses
known to contribute to inflammation-associated pathologic pregnancies. Our data also point to the involvement
of a human- and placenta-specific miRNA called miRNA-519c-3p (miR-519c) in the development of placental
immune tolerance. Our overriding hypothesis is that repeated exposure of the placenta to pathogens induces a
tolerant phenotype mediated by the miR-519c to guard the maternal-fetal interface from the exaggerated
inflammation associated with pathologic pregnancies. We hypothesize that LPS/LTA induce placental
trophoblasts to secrete miR-519c packaged within placental extracellular vesicles for delivery to nearby or
distant cells. The miR-519c within the EVs will mediate down-regulation of exaggerated pro-inflammatory
responses associated with repeated bacterial toxin exposures.
 We propose the following specific aims: Aim 1: Investigate the role of miR-519c in mediating immune
adaptation in the human placenta after repeated infections and Aim 2: Investigate the molecular mechanisms
of placental miR-519c mediating immune adaptation. These studies will set the stage for future experiments to
test if decreased expression of miR-519c is linked to inflammation-associated pathologic pregnancies. This
unique human- and placenta-specific miR-519c can be an excellent biomarker candidate as well as a
therapeutic targe...

## Key facts

- **NIH application ID:** 10795000
- **Project number:** 5R01HD098258-06
- **Recipient organization:** NEW YORK UNIVERSITY D/B/A NYU LONG ISLAND SCHOOL OF MEDICINE
- **Principal Investigator:** Nazeeh N Hanna
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $321,233
- **Award type:** 5
- **Project period:** 2020-04-02 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10795000

## Citation

> US National Institutes of Health, RePORTER application 10795000, Placenta-specific miR-519c-mediated induction of immune tolerance in human placenta (5R01HD098258-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10795000. Licensed CC0.

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