# Type 2 cytokines and innate lymphoid cells in pediatric ulcerative colitis

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2021 · $447,339

## Abstract

PROJECT SUMMARY
This proposal addresses two critical gaps in the treatment of pediatric ulcerative colitis (UC). The first gap is
the need for patient-specific immunologic profiles that inform precision UC treatments to achieve remission
efficiently on the safest medication. The second gap is the need to investigate therapeutic mechanisms that
promote epithelial homeostasis and, thereby, improve mucosal healing, one of the best predictors of sustained
remission in UC. We previously demonstrated that treatment naïve pediatric UC can be distinguished from
colon-only Crohn's disease by increased mucosal expression of type 2 and type 17 immune response genes,
as measured by a custom real time RT-qPCR microfluidic array. Furthermore, we observed that high mucosal
expression of the type 2 cytokines IL13 and IL5 was associated with 5-fold increased odds of 12-month clinical
remission in pediatric UC. We have also shown that IL33, a cytokine that induces type 2 cytokine production by
innate lymphoid cells (ILCs), is increased in pediatric UC and is protective in oxazolone colitis in mice, in part
through preservation of mucin-producing goblet cells. Maintenance of the mucus layer is critical for epithelial
barrier function and mucosal healing. Our preliminary data supports that IL33 induces goblet cell differentiation
by promoting the production of IL13 by group 2 ILCs (ILC2s). Our overarching hypothesis is that the induction
of mucosal type 2 cytokines by ILC2s in a subset of pediatric UC patients protects the epithelium in the setting
of uncontrolled type 17 inflammation and leads to superior treatment outcomes. In Aim 1, we will apply our
array to tissues from treatment-naïve patients in a large prospective pediatric UC inception cohort and validate
the type 2 gene expression signature for predicting treatment-specific clinical and endoscopic outcome. We will
also integrate our array data with microbiome and transcriptome data sets from this cohort to identify key
associations between type 2 immunophenotype and microbial colonization/function and host epithelial
homeostasis/repair pathways, respectively. In Aim 2, we will identify ILC2s as a key source of type 2 cytokines
in pediatric UC using multicolor flow cytometry and single-cell RNA sequencing. We will also determine the
effect of autologous peripheral blood ILC2s on human primary colonoid growth and differentiation using a
colonoid-immune cell co-culture system. In Aim 3, we will determine the effect of ILC2s on epithelial repair and
differentiation, and treatment response during chronic colitis in mice using the T cell transfer and chronic DSS
models. Upon completion of Aim 1, we will have validated an assessment of UC immunophenotype for
predicting clinical remission and mucosal healing in response to specific treatments in a large well-defined UC
inception cohort, which will inform precision patient-specific treatment in UC. Upon completion of Aim 2 and 3,
we will have determined whether ILC...

## Key facts

- **NIH application ID:** 10169427
- **Project number:** 5R01DK117119-04
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Michael J Rosen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $447,339
- **Award type:** 5
- **Project period:** 2018-07-18 → 2021-08-06

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10169427

## Citation

> US National Institutes of Health, RePORTER application 10169427, Type 2 cytokines and innate lymphoid cells in pediatric ulcerative colitis (5R01DK117119-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10169427. Licensed CC0.

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