# Reprogramming T Cells in Rheumatoid Arthritis

> **NIH VA IK2** · PORTLAND VA MEDICAL CENTER · 2022 · —

## Abstract

Rheumatoid arthritis (RA) is a chronic disease involving painful destruction of the joints and eventual loss of
function. Although its etiology remains unknown, genetic and experimental data strongly suggest deleterious
CD4+ T cell responses drive the pathogenesis of RA. Current treatment strategies aimed at modifying late-
stage consequences of inflammation do not correct underlying T cell defects and are therefore not curative.
Thus, a better understanding of intrinsic regulatory factors of arthritogenic T cells is warranted. The proposed
CDA, which encompasses hypothesis-driven research coupled with a multi-disciplinary training plan, will
enable me to reach my ultimate goal of integrating my prior training in host-directed therapeutics (HDT) with my
knowledge of biological processes that drive immunity, allowing me to advance new treatments for veterans
suffering from RA. My prior PhD training in the fields of microbial infection and HDT coupled with recent post-
doctoral training in translational medicine and preclinical animal models of arthritis have provided me with a
solid foundation upon which to build novel studies proposed in this application. I have gathered key preliminary
data in a preclinical model of RA (SKG mice) that supports the premise of this application; that NOD2 functions
as an endogenous negative regulator of TCR-mediated activation and pro-inflammatory responses of CD4+ T
cells in RA. The major goals of this application are to investigate how NOD2 controls TCR-mediated activation
and function of CD4+ T cells in RA (Aim1), and to elucidate how expression of NOD2 suppresses the
pathogenicity and alters the gene expression profile of a discrete subset of arthritogenic CD4+ T cells in SKG
mice (Aim2). Completion of this work will provide important mechanistic insight regarding the function of NOD2
in T cells from RA patients as well as reveal additional molecular pathways independent of NOD2 that control
arthritogenic T cell responses. Results from these studies will tell us whether we might be able to reprogram
aberrant T cells to stop inflammation and irreversible joint damage in RA patients. This study will serve as a
platform for future work in manipulation of TCR-signaling responses in RA. To gain clinical and laboratory skills
needed for this project, and to attain my goal of becoming an independent translational investigator at the VA
Portland Healthcare System (VAPORHCS), I have developed a training plan consisting of didactic coursework,
conferences, and laboratory experience that will be guided by an expert multidisciplinary mentoring team. The
VAPORHCS is a national leader in research with over 100 investigators and over 500 active research
proposals with an excellent track record of training junior investigators. The strong collaborative relationship
between VAPORHCS and the affiliated hospital and research center, Oregon Health & Science University
(OHSU), will allow me further access to collaborators, educatio...

## Key facts

- **NIH application ID:** 10477287
- **Project number:** 5IK2BX004523-04
- **Recipient organization:** PORTLAND VA MEDICAL CENTER
- **Principal Investigator:** RUTH NAPIER
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10477287

## Citation

> US National Institutes of Health, RePORTER application 10477287, Reprogramming T Cells in Rheumatoid Arthritis (5IK2BX004523-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10477287. Licensed CC0.

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