# Regulation of germinal centers by thymic stromal lymphopoietin in mice and humans

> **NIH NIH F32** · BENAROYA RESEARCH INST AT VIRGINIA MASON · 2020 · $65,310

## Abstract

PROJECT SUMMARY
 IgE antibodies to environmental proteins are detected in up to 40% of the worldwide population, and the
prevalence of allergic disease continues to rise in industrialized nations. Although several therapies can mitigate
antibody-driven anaphylaxis or block antibody effector functions, high mortality rates persist without a curative
treatment, and the mechanisms that control allergen-specific antibody production are still poorly understood.
Previous work from our group and others showed that Thymic Stromal Lymphopoietin (TSLP) is required for the
development allergic disease, and we recently discovered that TSLP also plays an additional role in controlling
IgE and IgG1 antibody production in germinal centers (GCs). GC B cells and T follicular helper cells upregulate
the expression of surface TSLP receptor (TSLPR) as they enter into the GC microenvironment, and TSLPR-
deficient mice produce significantly lower titers of antigen-specific IgG1 and IgE upon immunization. When CD4+
T cells specifically lack TSLPR expression (CD4creTSLPRF/F), immunized mice develop similar frequencies of
antigen-specific germinal centers, but lower numbers of IgG1-producing B cells with high-affinity for antigen,
suggesting that TSLPR expression on T cells may be required for affinity maturation in the germinal center.
Therefore, we hypothesize that Tfh cells and germinal center B cells differentially regulate germinal center activity
by two distinct mechanisms. Here, we will ask how TSLPR signaling in each of these cell populations
independently regulate the production of IgE/IgG1 antibodies in mouse models, and we will perform follow-up
experiments to confirm that TLSP-blocking therapy can reduce the number of allergen-specific plasma cells and
Tfh cells in patients with cat allergies. Overall, our research into the connection between TSLP receptor signaling
and allergen-specific germinal center responses could build a foundation to establish novel therapeutics to treat
or prevent the onset of allergic disease.

## Key facts

- **NIH application ID:** 10069011
- **Project number:** 1F32AI154787-01
- **Recipient organization:** BENAROYA RESEARCH INST AT VIRGINIA MASON
- **Principal Investigator:** Phillip P Domeier
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $65,310
- **Award type:** 1
- **Project period:** 2020-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10069011

## Citation

> US National Institutes of Health, RePORTER application 10069011, Regulation of germinal centers by thymic stromal lymphopoietin in mice and humans (1F32AI154787-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10069011. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*