# The Reprogramming of Regulatory T cells to a Th17 Phenotype in Systemic Juvenile Idiopathic Arthritis

> **NIH NIH K08** · BOSTON CHILDREN'S HOSPITAL · 2020 · $167,985

## Abstract

Project Summary/Abstract
The disease course of systemic onset juvenile idiopathic arthritis (sJIA) follows a peculiar pattern compared to
other forms of inflammatory arthritis observed in children. The initial phase of the disease is heralded by high
fevers, rash, and systemic inflammation, and only a subset of patients develops chronic arthritis. It is well
known that IL-1β and IL-6 are key mediators of the systemic symptoms in early sJIA. Our ultimate goals are to
better understand the factors that predispose some children to develop chronic arthritis in sJIA so that we can
identify effective treatments and strategies to prevent arthritis in this condition altogether.
This proposal outlines a research and training plan with a focus on regulatory T cell dysfunction as a mediator
of arthritis in sJIA. The investigator conducted preliminary studies that showed abnormalities in Treg cells from
patients with acute sJIA, including markedly increased IL-17 production and decreased frequencies of
peripherally-induced Treg cells. Based on these findings and the known permissive effects IL-1β and IL-6 have
on Th17 polarization, we hypothesize that the inflammatory cytokine environment in early sJIA transforms Treg
cells into Th17-like-effector cells and blocks peripherally-induced Treg differentiation. The result is a Th17/Treg
imbalance then drives chronic arthritis in sJIA. The proposed Specific Aims will test this hypothesis with human
biosamples. In Aim 1, Treg stability and phenotype in sJIA will be determined through the use of mass
cytometry, transcriptomics, and DNA methylations studies. Aim 2 evaluates the effects of IL-1β and IL-6 on
Treg suppressive capacity and peripherally-induced Treg generation from naïve CD4+ T cells.
Using multidimensional immunoprofiling made possible by innovative technologies and functional assays, this
project will allow the candidate to develop important skills that will provide the foundation for an independent
research career. In the short term, the candidate’s goals are to develop a deeper understanding of Treg-
mediated tolerance, leverage cutting-edge techniques such as mass cytometry and RNA sequencing to study
patient samples, and master bioinformatic approaches to analyze large data sets. A team of mentors, advisors,
and collaborators with the requisite expertise has been assembled to ensure success and allow the applicant
to meet the ultimate objective of independence as a translational investigator in the field of pediatric
rheumatology.

## Key facts

- **NIH application ID:** 9894736
- **Project number:** 5K08AR073339-03
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Lauren A Henderson
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $167,985
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9894736

## Citation

> US National Institutes of Health, RePORTER application 9894736, The Reprogramming of Regulatory T cells to a Th17 Phenotype in Systemic Juvenile Idiopathic Arthritis (5K08AR073339-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9894736. Licensed CC0.

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