# T peripheral regulatory cells as modulators of T cell-B cell interactions in arthritis

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2024 · $492,123

## Abstract

PROJECT SUMMARY/ABSTRACT
T cell-B cell interactions that result in B cell maturation and antibody production were once thought to occur
exclusively in lymphoid organs. It is now appreciated that T peripheral helper (Tph) cells provide excessive
help to B cells resulting in autoantibody production in inflamed peripheral tissues. Such disordered Tph cell-B
cell responses have been implicated in some forms of chronic inflammatory arthritis in both adults and children.
The pathways that regulate the Tph cell-B cell axis in non-lymphoid tissues are not understood.
By studying joint fluid from patients with juvenile idiopathic arthritis (JIA), we found evidence of dysregulated
Tph cell-B cell responses in children with early-onset and anti-nuclear antibody (ANA) positive forms of the
disease. Our preliminary studies also identified a novel T cell subset, T peripheral regulatory (Tpr) cells, in
the joints of patients with JIA. These Tpr cells co-express regulatory T (Treg) and B cell-helper T cell factors.
Further, Tpr cells have the ability to inhibit Tph cell-B cell interactions that result in plasmablast generation in
our T cell-B cell co-culture system. The central hypothesis of this application is that Tpr cells restrain Tph cell-B
cell interactions in the joints of patients with inflammatory arthritis.
The central hypothesis in this research proposal will be tested with two Specific Aims that will be conducted
with biosamples (peripheral blood, synovial fluid, tonsil tissue) from children with JIA as well as healthy
controls. Through our established T cell-B cell co-culture system, Aim1 will assess the mechanisms by which
Tpr cells regulate Tph cell-B cell interactions. We will test the hypothesis that Tpr cells are uniquely equipped
to inhibit proliferation and cytokine production in B cell-helper T cells as well as antibody production, class
switching, and maturation in B cells by inducing alterations in gene expression and metabolism. Using a
multiomics approach coupled with functional assays, Aim 2 will define the developmental pathways and
transcriptional program required for Tpr functionality. We will test the hypothesis that Tpr cells differentiate from
Treg cells in the joint and have a unique transcriptional program that is distinct from other Treg subsets and
ensures Tpr functionality in tissues.
The research is innovative because we will use a systems immunology approach coupled with synovial fluid
samples from children with JIA to study T cell-B cell responses directly from affected tissues. Completion of
this research will be significant because Tpr cells represent a novel regulatory pathway with the capacity to
restrain Tph cell-B cell responses and ameliorate tissue-specific inflammation in arthritis and other autoimmune
diseases.

## Key facts

- **NIH application ID:** 10779359
- **Project number:** 1R01AR083424-01
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Lauren A Henderson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $492,123
- **Award type:** 1
- **Project period:** 2023-12-15 → 2028-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10779359

## Citation

> US National Institutes of Health, RePORTER application 10779359, T peripheral regulatory cells as modulators of T cell-B cell interactions in arthritis (1R01AR083424-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10779359. Licensed CC0.

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