# Role of Gut Protist Derived Compounds on Dietary Antigen Presenting Dendritic Cells in Celiac Disease

> **NIH NIH F31** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $46,465

## Abstract

PROJECT SUMMARY/ABSTRACT
 The mucosal immune system fosters a delicate regulatory environment which provides protection from
gastric pathogens while maintaining oral tolerance to food. Tolerance to food antigens occurs through the
induction of peripheral regulatory T cells (pTreg) and their regulatory suppressive functions. Moreover, dendritic
cells (DCs) play a central role in maintaining tolerance to dietary antigens. However, enteric virus infections, like
reovirus, can elicit pathological processes leading to the initiation of T helper 1 (Th1) immunity against dietary
gluten resulting in loss of oral tolerance (LOT) and celiac disease (CeD). CeD is a digestive disorder
characterized by an inflammatory CD4 T helper 1 (Th1) immune response to dietary gluten found in wheat,
barley, and rye. Even though 30% of people carry the genetic alleles predisposing to CeD, only 1% develop
disease, suggesting that additional genetic and environmental factors such as enteric viral infections contribute
to pathogenesis. The high prevalence of CeD and the challenges associated with maintaining a gluten-free diet
make CeD a significant burden in modern health care. New strategies to promote oral tolerance and to prevent
or revert LOT in CeD patients upon exposure to gluten antigens are still needed. We hypothesized that certain
gut microbes have the capacity to protect against virus-mediated LOT and development of CeD. By using our
previously defined virus mediated LOT CeD model, we discovered that the gut colonizing protist Tritrichomonas
arnold (T. arnold) promotes oral tolerance and protects against virus-mediated LOT. Moreover, our studies using
human stool samples support a role for Tritrichomonas spp. colonization in protecting against development of
CeD. Mechanistically, our findings show that T. arnold promotes oral tolerance by engaging dietary antigen
presenting DCs and restraining the reovirus induced proinflammatory program of dietary antigen presenting DCs
and thus limit their ability to promote Th1 immune responses. In this proposal we will use conceptually and
technically innovative approaches to further gain insights in how T. arnold-derived compounds modulate dietary
antigen presenting DC responses under homeostatic conditions and inflammatory microbial triggers.
Furthermore, using our LOT CeD mouse model we will interrogate a druggable candidate pathway identified in
our T. arnold DC-RNA-sequencing screen that has been associated with tolerogenic immune responses. The
findings of this proposal will provide insights into novel approaches for preventing LOT in at-risk individuals and
re-establishing oral tolerance to gluten in CeD patients.

## Key facts

- **NIH application ID:** 10821844
- **Project number:** 1F31DK138621-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Luzmariel Medina-Sanchez
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $46,465
- **Award type:** 1
- **Project period:** 2024-06-01 → 2025-04-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10821844

## Citation

> US National Institutes of Health, RePORTER application 10821844, Role of Gut Protist Derived Compounds on Dietary Antigen Presenting Dendritic Cells in Celiac Disease (1F31DK138621-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10821844. Licensed CC0.

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