# Alteration of function and specificity of TFH in SLE

> **NIH NIH R01** · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · 2022 · $547,589

## Abstract

Project Summary/ Abstract
Systemic lupus erythematosus (SLE) is a chronic and complex autoimmune disease and
pathogenic mechanisms are not well understood. Based on data from SLE patients and GWAS,
we developed a mouse model to phenocopy the expression pattern of the PRDM1 risk allele.
Mice with a selective deficiency of BLIMP1 in dendritic cells (DCs) (Prdm1 CKO mice) develop
SLE with an increased number of T follicular helper cells (TFH) and autoantibodies arising in a
germinal center response. Only female mice develop disease. The central hypothesis for the
proposed studies is that BLIMP1-deficient DCs alter the selection of T cells in the thymus. We
further hypothesize that estrogen and estrogen-receptor mediated signaling play a critical role in
BLIMP1-deficient DC function, altering antigen presentation and synergizing with BLIMP1
deficiency to skew to TFH differentiation. The following aims will address these hypotheses. Aim
1 will determine if the altered TFH repertoire in female Prdm1 CKO mice is determined during
thymic selection. We will identify whether BLIMP1-deficient DCs alter the strength of TCR
signaling to alter the T cell repertoire. We will explore the function of TFH in female Prdm1 CKO
mice and female control mice, and their activation of autoreactive B cells. Aim 2 will
investigate functional changes in DCs and TFH conferred by estrogen receptor signaling. These
studies should suggest therapeutic strategies in a defined subset of SLE patients, and
advance precision medicine in a disease where many agree that the failure of clinical
trials reflects an inadequate understanding of patient heterogeneity.

## Key facts

- **NIH application ID:** 10437692
- **Project number:** 5R01AR074565-04
- **Recipient organization:** FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
- **Principal Investigator:** Betty Diamond
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $547,589
- **Award type:** 5
- **Project period:** 2019-07-05 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10437692

## Citation

> US National Institutes of Health, RePORTER application 10437692, Alteration of function and specificity of TFH in SLE (5R01AR074565-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10437692. Licensed CC0.

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