# LR-IL-22 for Mitigation and Management of Radiation Injuries

> **NIH NIH U01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $99,639

## Abstract

Abstract:
Mitigation of damage caused by total body irradiation (TBI) or partial body irradiation (PBI) requires targeting
the acute gastrointestinal syndrome. Parenteral administration of radiation mitigators for the hematopoietic
syndrome may also ameliorate the gastrointestinal syndrome; however, drug delivery to the intestinal crypts is
ineffective due to irradiation damage to the intestinal microvasculature. We have demonstrated that oral
administration of engineered Lactobacillus reuteri, which produces and releases IL-22 (LR-IL-22), ameliorates
the TBI induced acute gastrointestinal syndrome. Effective mitigation is associated with preservation of Lgr5+
intestinal crypt stem cells and their regeneration capacity. We will now establish the underlying mechanism of
radiation mitigation by LR-IL-22, and will develop a microbial therapeutic with enhanced safety and efficacy.
Preliminary data demonstrate that LR-IL-22 restores irradiation-induced suppression of gene transcription in
Lgr5+ stem cells. TBI reduces expression of the aryl hydrocarbon receptor (AhR) in the intestine and its
generation of downstream products, including IL-22. We hypothesize that TBI-induced intestinal damage will
be further mitigated by combining LR-IL-22 with a probiotic (R2Ic) that naturally induces AhR to stimulate
recovery of intrinsic IL-22 levels. Furthermore, we will establish that priming the release of IL-22 by our
engineered probiotic increases therapeutic efficacy and the biological and environmental safety profiles. The
First Specific Aim tests the hypothesis that LR-IL-22 restores radiation suppressed transcription at the
molecular level in Lgr5+GFP+ intestinal stem cells. The Second Specific Aim tests the hypothesis that the
activation of AhR in irradiation weakened cells by LR-IL-22 is further boosted by oral gavage of R2Ic to induce
intrinsic IL-22 production. The Third Specific Aim addresses the need to provide biological and
environmental containment of LR-IL-22, while improving the therapeutic efficacy. Successful completion of the
proposed studies will lead to translation of LR-IL-22 to the National stockpile, as an effective mitigator of the
acute radiation induced gastrointestinal syndrome.

## Key facts

- **NIH application ID:** 11013947
- **Project number:** 3U01AI172885-02S1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** JOEL S GREENBERGER
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $99,639
- **Award type:** 3
- **Project period:** 2022-12-20 → 2027-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11013947

## Citation

> US National Institutes of Health, RePORTER application 11013947, LR-IL-22 for Mitigation and Management of Radiation Injuries (3U01AI172885-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11013947. Licensed CC0.

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