# Newly Identified T Peripheral Helper (Tph) Cells in Rheumatoid Arthritis

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $500,323

## Abstract

Rheumatoid arthritis (RA) is a prototypical autoimmune disease characterized by
activation of autoreactive T cells and B cells, production of autoantibodies, and accumulation of
lymphocyte aggregates within the synovium. Recently, we described a population PD-1hi CD4+
T cells that we called T `peripheral helper' (Tph) cells that is markedly expanded within RA
synovium and possesses the capacity to infiltrate inflamed tissues and promote B cell
maturation and antibody production (Rao et al., Nature, 2017). Tph cells share several features
with T follicular helper (Tfh) cells, the principal T cell subset known to drive B cell maturation in
secondary lymphoid tissues. Like Tfh cells, synovial Tph cells express high levels of IL-21,
which promotes B cell survival, and CXCL13, a B cell chemoattractant. Yet, Tph cells differ from
Tfh cells in expression of chemokine receptors for homing to inflammatory sites and in
transcriptional regulators.
 The discovery of Tph cells has clinical implications for diseases that involve
autoantibody production within tissues, including RA and SLE. Selective targeting of Tph cells
could potentially interrupt local production of autoantibodies and downstream inflammatory
cascades. However, such targeting will require a precise characterization of the phenotype of
pathologic Tph cells and a more complete understanding of the factors that drive Tph cell
differentiation and expansion. Our current knowledge of Tph cells is limited.
 We propose in Aim 1 to define the heterogeneity and subpopulations of Tph cells using
unbiased single cell transcriptomics followed by isolation of distinct subpopulations for functional
analysis including cytokine production. In Aim 2, we gain insight into how cytokine signaling
may alter Tph cells in vivo by tracking changes in Tph cell numbers and function in response to
currently used targeted therapies for RA. Finally, in Aim 3 we determine what drives Tph cell
differentiation and maturation. Together, these studies will advance our knowledge of the
nature of newly identified Tph cells in RA and provide information critical to understanding their
role in the immunopathogenesis of RA and potential applications for therapy.

## Key facts

- **NIH application ID:** 10197753
- **Project number:** 5R01AR073290-04
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Michael B. Brenner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $500,323
- **Award type:** 5
- **Project period:** 2018-09-13 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10197753

## Citation

> US National Institutes of Health, RePORTER application 10197753, Newly Identified T Peripheral Helper (Tph) Cells in Rheumatoid Arthritis (5R01AR073290-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10197753. Licensed CC0.

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