# Epigenetic Mechanisms of T Cell Dysregulation in PTSD

> **NIH NIH R01** · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · 2020 · $470,863

## Abstract

Post-traumatic stress disorder (PTSD) is an adverse psychiatric condition that occurs after
exposure to extremely stressful life events. PTSD patients also develop a variety of disorders
with an inflammatory component. While majority of the studies indicate that there is an
excessive inflammatory state in PTSD, the precise mechanisms of immunomodulation seen
during PTSD are not clear. Recently, we have made an exciting observation that the severity of
PTSD is correlated with greater inflammation and a broadly dysregulated microRNA (miR)
profile with numerous targets that regulate inflammatory T cell response. Specifically, we noted
that numerous downregulated miRs in PTSD patients targeted components of the nuclear factor
of activated T cells (NFAT) pathway, crucial for the activation, proliferation and differentiation of
T cells. In addition to the NFAT proteins themselves, the serine-threonine protein phosphatase
calcineurin subunits A (isoforms PPP3CA, PPP2CB, and PPP3CC) and B (isoforms PPP3R1
and PPP3R2), which activate NFAT through dephosphorylation, were found to serve as targets
for numerous dysregulated miRs in PTSD patients. The status of the T cell regulation, and in
particular, the NFAT pathway in PTSD has not been evaluated thus far. Based on our
preliminary studies, we will test the central hypothesis that PTSD associates, at least in
part, with dysregulation in the epigenetic mechanisms that alter NFAT signaling pathway
leading to a pro-inflammatory state. We will pursue these studies trauma-exposed PTSD
patients when compared to trauma-exposed non-PTSD controls. We will pursue 3 specific aims:
Aim 1: We will identify the mechanisms through which miR dysregulation leads to alterations in
NFAT signaling pathway leading to an inflammatory state in PTSD patients. Aim 2: We will
determine whether PTSD triggers differential DNA methylation of specific miR and/or targets of
NFAT signaling pathway components in T cells leading to pro-inflammatory response. Aim 3:
We will test the role of histone modifications in the expression of miRs on NFAT components in
PTSD patients.
 Together, our studies will delineate the epigenetic mechanisms underlying signaling
pathways that lead to alterations in NFAT signaling and consequent T cell dysregulation and
excess inflammation in PTSD patients. Our studies also aim to identify epigenetic biomarkers of
PTSD that will help in the early diagnosis and treatment.

## Key facts

- **NIH application ID:** 9812833
- **Project number:** 5R01AI129788-04
- **Recipient organization:** UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
- **Principal Investigator:** Mitzi Nagarkatti
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $470,863
- **Award type:** 5
- **Project period:** 2016-11-15 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9812833

## Citation

> US National Institutes of Health, RePORTER application 9812833, Epigenetic Mechanisms of T Cell Dysregulation in PTSD (5R01AI129788-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9812833. Licensed CC0.

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