# Regulation of Tfh function in autoimmunity by TSLP

> **NIH NIH R21** · BENAROYA RESEARCH INST AT VIRGINIA MASON · 2022 · $259,451

## Abstract

Project Summary
 Germinal centers (GCs) are dynamic immune microarchitectures that expand in secondary lymphoid
organs during infection or immunization. GCs can also develop in the absence of overt immunization or
detectable adventitious infection (called spontaneous GCs, Spt-GCs). As opposed to induced GCs that form
during immunization or anti-pathogen responses, Spt-GCs develop in response to endogenous antigens and
contribute, in part, to chronic autoimmunity. Spt-GCs are enlarged and more frequent in autoimmune-prone mice
in the absence of detectable pathogens or overt immune challenge. Spt-GCs exhibit a linear correlation with
nuclear-reactive autoantibody titers in lupus-prone mice and many GC B cells isolated from Spt-GCs developed
in SLE-prone mice are autoreactive. Both Tfh cells and CGC B cells within the Spt-GCs play essential roles in
regulating high-affinity autoantibody production.
 Spt-GCs have also been detected in patients with several different autoimmune diseases including
Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), Multiple Sclerosis (MS), Sjogren’s syndrome
(SS) and Type 1 diabetes (T1D). For example, pediatric SLE patients have elevated numbers of circulating pre-
GC B cells and adult SLE patients exhibit increased circulating Tfh cells. These data indicate the important roles
that Spt-GCs play in pathogenic autoantibody production.
 While the correlation of Spt-GCs with autoimmunity is clear, the factors that control their development
remain obscure. We have found that the cytokine thymic stromal lymphopoietin (TSLP) plays a significant role
in the development of Spt-GCs. TSLP- and TSLPR-deficient mice have dramatically reduced numbers of Spt-
GCs, and those that exist appear to be vestigial. Consistent with this observation, we have also found that TSLP
signaling is critical for the differentiation of Tfh. Taken as a whole, these data demonstrate an important role for
TSLP in Spt- and induced-GC formation and function. We will test this hypothesis by determining the role of
TSLP in Tfh development and function (Aim 1), and determine the role of Tfh-specific TSLP signaling in
autoimmune prone mice.

## Key facts

- **NIH application ID:** 10441850
- **Project number:** 1R21AI169418-01
- **Recipient organization:** BENAROYA RESEARCH INST AT VIRGINIA MASON
- **Principal Investigator:** Steven F Ziegler
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $259,451
- **Award type:** 1
- **Project period:** 2022-02-15 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10441850

## Citation

> US National Institutes of Health, RePORTER application 10441850, Regulation of Tfh function in autoimmunity by TSLP (1R21AI169418-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10441850. Licensed CC0.

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