# UPIT: Unleash the Potential of Intestinal Transplantation

> **NIH NIH R01** · GEORGETOWN UNIVERSITY · 2021 · $479,946

## Abstract

Abstract
Intestinal transplantation (ITx) has emerged as a key, but under-utilized and under-studied, therapeutic option
for patients suffering from intestinal failure. Specifically, while an estimated 40,000 patients could benefit from
ITx, a mere 141 ITx transplants were performed in the United States in 2015; the country's lowest volume solid
organ transplant. This low volume is due to poor patient and allograft survival after ITx when compared to other
fields of solid organ transplantation as this transplant is associated with the transplantation of the largest
immune cell and microbial load of any solid organ. Because there is a high risk of allograft enteropathy/
immunological graft loss, strong regimens of generalized immunosuppression are typically applied, which lead
to high morbidity and mortality. The result is a catch-22: if ITx is performed, the risk of rejection is high, which
leads to over-immunosuppression, which results in complications and high treatment costs, which dissuades
ITx from being offered in the first place.
To untangle this catch-22 and unleash the potential of ITx, this project will leverage the fact that we are the
leading ITx center in the country and lay the groundwork for a targeted immunotherapy approach to prevent/
control allograft enteropathy with minimization of generalized immunosuppression. Preliminary data has
revealed that both the adaptive and innate immune systems are key players in stable allograft function and
allograft enteropathy and as such, this project's three specific aims will focus on both systems:
 1. To determine the roles and mechanisms of proinflammatory Th17 and protective regulatory T cell
 (Treg) responses in human ITx recipients with stable allograft function versus enteropathy
 2. To determine the roles and mechanisms of proinflammatory type 1 innate lymphoid cell (ILC1)
 and protective type 3 innate lymphoid cell (ILC3) responses in human ITx recipients with stable
 allograft function versus enteropathy
 3. To elucidate the crosstalk between the master regulators NOD2 (antimicrobial sensor) and CD39
 (purinergic signaling) and innate and adaptive immune responses in human ITx recipients with
 stable allograft function versus enteropathy
These three aims will lay the foundation for improving outcomes and quality of life for several patient groups:
(A) patients who are on home-based TPN regimens could be considered for ITx, ideally before complications
worsen that jeopardize the outcomes of ITx; (B) new and past recipients of ITx could avoid the life
threatening complications from generalized immunosuppression, which will be especially beneficial for children
who receive ITx in their earliest years of life; and (C) patients suffering from IBD could benefit from new
therapeutic insights as we hypothesize that IBD is influenced by similar factors that modulate ITx enteropathy.

## Key facts

- **NIH application ID:** 10141194
- **Project number:** 5R01AI132389-05
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **Principal Investigator:** Alexander Helmut Kurt Kroemer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $479,946
- **Award type:** 5
- **Project period:** 2017-05-05 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10141194

## Citation

> US National Institutes of Health, RePORTER application 10141194, UPIT: Unleash the Potential of Intestinal Transplantation (5R01AI132389-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10141194. Licensed CC0.

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