# IL-37: a novel regulator of inflammation in CNS autoimmunity

> **NIH NIH R01** · THOMAS JEFFERSON UNIVERSITY · 2021 · $390,000

## Abstract

SUMMARY
 Current “disease-modifying drugs” for MS have changed the course of disease with decrease in
relapse and possible slowing of the progression. however, many patients eventually experience
relapses and/or disease progression. There is thus a clearly unmet need for developing safer and
more effective MS therapies. IL-37, a member of the IL-1 family of cytokines, has been recently
recognized as a novel immunoregulatory cytokine. Importantly, IL-37 exerts its function through a
“dual-effect” property, i.e., both as a secreted cytokine that will act through its receptor IL-37R (SIGIRR
and IL-18Ra) and as a transcription factor, and this distinct property may make IL-37 a more powerful
immunomodulator than most conventional cytokines for clinical application. Based on the literature and
our preliminary observations, we hypothesize that IL-37 is a key regulator of inflammation in CNS
autoimmunity through induction of amphiregulin, a tissue-repair associated cytokine with
immunomodulatory properties. To test this hypothesis, we propose the following specific aims: (1) To
define IL-37R expression and IL-37 responsiveness in immune cells of MS patients. We will first
identify the source(s) of IL-37 and compare IL-37R expression and responsiveness to IL-37 in immune
cells of MS patients vs. healthy controls. We will also test our hypothesis that IL-37 treatment will block
proinflammatory monocyte- or Th1/Th17 cell-induced demyelination, using a novel organotypic slice
culture system of adult human brain tissue. (2) To determine the effect of IL-37 on CNS resident cells
during autoimmune neuroinflammation. We will first test the effect of IL-37 on microglia, astrocytes and
oligodendrocytes of murine and human origin. We will then determine the expression of IL-37R in CNS
resident cells from patients with MS. Finally, we will test if upregulation of the IL-37R (TIR8 subunit)
suppresses neuroinflammation. 3) To investigate the induction of the amphiregulin pathway as a
possible mechanism of IL-37 action. This will be tested in amphiregulin conditional knockout EAE mice
and monocytes and T/B cells of healthy subjects and. MS patients.
 Information gained from these studies could result in a better understanding of pathogenic
mechanisms of MS and in the development of new strategies for regulating the immune response in
order to stop the progression of this disease, and likely other autoimmune diseases.

## Key facts

- **NIH application ID:** 10199564
- **Project number:** 1R01AI160189-01
- **Recipient organization:** THOMAS JEFFERSON UNIVERSITY
- **Principal Investigator:** A.M. Rostami
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $390,000
- **Award type:** 1
- **Project period:** 2021-03-11 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10199564

## Citation

> US National Institutes of Health, RePORTER application 10199564, IL-37: a novel regulator of inflammation in CNS autoimmunity (1R01AI160189-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10199564. Licensed CC0.

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