The GI tract in Systemic Alloimmunity
NIAID - National Institute of Allergy and Infectious Diseases
About This Grant
ABSTRACT/PROJECT SUMMARY Acute Graft-versus-Host Disease (aGVHD) remains a critical barrier to clinical success after allogeneic hemato- poietic cell transplantation (allo-HCT) in patients with high-risk hematologic malignancies and non-malignant diseases. The current treatment options are limited and rely heavily on non-specific immunosuppression with high-dose glucocorticoids, which is only partially effective while increasing infection risk and potentially abating the protective Graft-versus-Leukemia (GVL) effect. Emerging evidence highlights the gastrointestinal (GI) tract as a pivotal driver of systemic alloimmunity, but the exact biological pathways involved in the interface between the GI tract and the immune system are incompletely understood, which impedes the development of novel targeted anti-aGVHD approaches. This proposal seeks to investigate the mechanisms of GI-driven T cell repro- gramming during aGVHD to identify novel therapeutic targets. We hypothesize that GI-derived T cells mediate systemic aGVHD-induced immunopathology while being dispensable for the GVL effect, which we will test in the three Specific Aims. Aim 1 will examine how GI-driven reprogramming impacts donor T cell pathogenicity. We will use photoconvertible Dendra2 donor mice to trace, profile, and functionally characterize GI-reprogrammed T cells as they traffic to distal organs during multiorgan aGVHD. Aim 2 will evaluate genetic (Itgb7-mutant T cells) and pharmacologic (anti-MadCAM-1 antibodies) strategies to block T cell trafficking to the GI tract, thereby mitigating extra-GI immunopathology in skin/esophageal aGVHD model induced by transplantation of OVA-spe- cific OT-I T cells to B6-K14.OVA recipient mice with keratinocyte-restricted OVA expression. Aim 3 will employ allo-HCT models in which aGVHD and GVL are mediated by distinct T cell subsets to determine whether GI- driven reprogramming affects the cytotoxic function of tumor-specific T cells in vivo. This project will provide foundational insights into tissue-specific immune regulation and inform the development of precision therapies to control aGVHD while preserving GVL. These findings promise broader relevance to T cell-mediated alloim- mune and autoimmune diseases, paving the way for clinical translation.
Grant Summary
The GI tract in Systemic Alloimmunity is a NIAID - National Institute of Allergy and Infectious Diseases grant providing up to $436K for university, nonprofit, healthcare org. Applications are due 2028-01-31 (open). Check eligibility and apply with FindGrants.
Focus Areas
Eligibility
How to Apply
Up to $436K
2028-01-31
- 1Confirm your organization is eligible for The GI tract in Systemic Alloimmunity from NIAID - National Institute of Allergy and Infectious Diseases, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NIAID - National Institute of Allergy and Infectious Diseases before the deadline.
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The GI tract in Systemic Alloimmunity: Frequently Asked Questions
Who is eligible for the The GI tract in Systemic Alloimmunity?
The GI tract in Systemic Alloimmunity is offered by NIAID - National Institute of Allergy and Infectious Diseases and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the The GI tract in Systemic Alloimmunity provide?
The GI tract in Systemic Alloimmunity provides up to $436K per award from NIAID - National Institute of Allergy and Infectious Diseases. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the The GI tract in Systemic Alloimmunity deadline?
Applications for The GI tract in Systemic Alloimmunity are due 2028-01-31 (open). Because deadlines can change, verify the date with the funder, NIAID - National Institute of Allergy and Infectious Diseases, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the The GI tract in Systemic Alloimmunity?
To apply for The GI tract in Systemic Alloimmunity, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIAID - National Institute of Allergy and Infectious Diseases.