# The role of IL-37 in human regulatory T cells

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2022 · $593,976

## Abstract

PROJECT SUMMARY/ABSTRACT
Understanding peripheral tolerance and the maintenance of immune system homeostasis are vital in the
control of human diseases. We have previously demonstrated that anti-inflammatory cytokine IL-37
participates in immune tolerance by generating semi-mature tolerogenic dendritic cells (DCs) in antigen-
specific adaptive immune responses. IL-37 is one of eleven IL-1 family members and the only known member
to be broadly anti-inflammatory. In our recent project, we found IL-37 levels were elevated in multiple human
immune cell types, specifically in regulatory T cells (Tregs) cells. Further analysis revealed that human Treg
cells express the highest IL-37 levels among all T-cell subsets and that intracellular expression of IL-37
correlates with the expression of master transcriptional regulator, FOXP3, in human Treg cells. Our current
project hypothesizes that elevated IL-37 expression stabilizes Treg cells and induces potent immune
suppression by controlling FOXP3 expression. IL-37 is not expressed in mice, but using transgenic mice and
peripheral blood T cells from human donors, we generated strong preliminary data to support our hypothesis.
In this grant proposal, we will use human primary Treg cells and T cell lines overexpressing IL-37 and its
mutant form to elucidate the biological and molecular mechanisms of IL-37 in controlling human Treg cell
function. Since our proposal uses human T cells, the results could be easily translated into clinical medicine
and patient care. Our findings will have an immense translational impact on many human diseases such as
autoimmunity and transplantation.

## Key facts

- **NIH application ID:** 10445346
- **Project number:** 5R01AI156534-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Mayumi Fujita
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $593,976
- **Award type:** 5
- **Project period:** 2021-07-06 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10445346

## Citation

> US National Institutes of Health, RePORTER application 10445346, The role of IL-37 in human regulatory T cells (5R01AI156534-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10445346. Licensed CC0.

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