# Tfh cells in Human Myositis

> **NIH NIH R21** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2021 · $229,391

## Abstract

ABSTRACT:
Dermatomyositis (DM) is a severe idiopathic inflammatory myopathy, associated with significant morbidity and
mortality. While the immunopathogenesis of DM is not fully understood, we have recently shown that interferon
chemokine signatures track with changes in disease activity in patients with DM [1]. Another feature of active
disease in DM is elevation of circulating T follicular helper (Tfh) cells [2, 3]. We recently studied circulating Tfh
cells (CXCR3neg Tfh2/17 and CXCR3pos Tfh1) from DM patients and healthy controls using single cell RNA
sequencing. We found that the Tfh2/17 cells had a type I interferon (IFN) signature, while the Tfh1 cells
upregulated genes in the type II IFN pathway. The Tfh cells from DM patients had higher expression of factors
that promote B-cell survival. Examining muscle biopsies from DM patients, we found extrafollicular Tfh and Tfh-
like cells in very close proximity to B-cells in the muscle tissue when compared to other T cell types. These data
suggest that Tfh and Tfh-like cells are pathogenic, promoting B cell activity in human DM muscle tissue.
The lymphoid aggregates observed in DM muscle biopsies are a classical finding, but the immunological
significance of these aggregates is not well understood. Recent studies have documented a number of Tfh-like
cells in tissues that can provide B cell help in extra-follicular lymphoid aggregates, in addition to classical Tfh
cells. We hypothesize that extrafollicular Tfh or Tfh-like cells are active in within lymphoid aggregates in DM
muscle, providing B cell help and inducing local expansion of B cells. This may be stimulated by the type I and
type II interferon pathways that are suggested by our preliminary data from circulating Tfh cells. Documenting
this phenomenon in the lymphoid aggregates in JDM muscle tissue could suggest specific interventions directed
at the T:B cell infiltrates that characterize active inflammation.
Via the studies proposed, we will define the functional activity of circulating cells capable of providing B cell help
in myositis, including Tfh and Tfh-like cells. It seems likely that extrafollicular T:B interactions are important in
human myositis, and in Aim 1 we will be able to compare the effectiveness of Tfh vs. Tfh-like cells from human
patients in providing B cell help. In Aim 2, we will comprehensively examine Tfh subsets in human muscle tissue
using an advanced method that will allow for quantitation of the various Tfh subsets as well as full transcriptome
assessment. The B cell receptor sequences will allow us to assess B cell clonality and local expansion, which
would provide further evidence of B cell help in the tissue.

## Key facts

- **NIH application ID:** 10232718
- **Project number:** 1R21AR078416-01A1
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Timothy B Niewold
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $229,391
- **Award type:** 1
- **Project period:** 2021-04-05 → 2022-01-25

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10232718

## Citation

> US National Institutes of Health, RePORTER application 10232718, Tfh cells in Human Myositis (1R21AR078416-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10232718. Licensed CC0.

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