Cytotoxic T cells and the epithelium in celiac disease
NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases
About This Grant
Project Summary Celiac disease (CD), a disease of small intestinal inflammation, is one of the most common autoimmune diseases with estimated worldwide prevalence >1%. Beyond a lifelong gluten free diet, treatment options for CD are limited. In most cases, the antigen(s) triggering human autoimmune disease is not known, severely hampering our mechanistic understanding of how these diseases are initiated or sustained. The exception is CD. In CD, the triggering antigen is dietary gluten, which activates gluten-specific CD4+ T cells. Not only is the antigen trigger in CD known, but its exposure can be controlled, providing truly unique opportunities to study human autoimmunity. The critical question of how a CD4+ T cell response directed against dietary gluten culminates in self-tissue damage by cytotoxic CD8+ αβ and γδ T cells, which are not thought to recognize gluten themselves, remains unanswered. The current model for celiac pathogenesis posits that cytotoxic CD8+ αβ and γδ T cell activation occurs downstream of CD4+ T cell-driven inflammation. Our preliminary data inform a revised model for CD pathogenesis, which will be applicable in autoimmune diseases beyond CD. Our central hypothesis to explain CD-mediated tissue destruction is that gluten-specific CD4+ T cells and cytotoxic T-IELs activate in parallel following gluten ingestion, with the latter cell population requiring additional tissue-derived signals for full activation. A critical aspect of our model is that CD4+ and CD8+ and γδ T-IELs have different antigen specificities. To investigate these hypotheses and dissect mechanisms through which an aberrant CD4+ T cell response to gluten culminates in specific tissue damage by cytotoxic T-IELs, we propose the following Aims. Aim 1. Dissect mechanisms through which gluten modulates Natural T-IEL populations in CD. Aim 2. Dissect the role of tissue- derived factors in unleashing the cytotoxic capacity of T-IELs in CD. Successful completion of these aims will advance our mechanistic understanding of CD and autoimmunity, and could inform novel therapeutic strategies.
Grant Summary
Cytotoxic T cells and the epithelium in celiac disease is a NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases grant providing up to $821K for university, nonprofit, healthcare org. Applications are due 2031-02-28 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $821K
2031-02-28
- 1Confirm your organization is eligible for Cytotoxic T cells and the epithelium in celiac disease from NIDDK - National Institute of Diabetes and Digestive and Kidney 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 NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases before the deadline.
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Cytotoxic T cells and the epithelium in celiac disease: Frequently Asked Questions
Who is eligible for the Cytotoxic T cells and the epithelium in celiac disease?
Cytotoxic T cells and the epithelium in celiac disease is offered by NIDDK - National Institute of Diabetes and Digestive and Kidney 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 Cytotoxic T cells and the epithelium in celiac disease provide?
Cytotoxic T cells and the epithelium in celiac disease provides up to $821K per award from NIDDK - National Institute of Diabetes and Digestive and Kidney 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 Cytotoxic T cells and the epithelium in celiac disease deadline?
Applications for Cytotoxic T cells and the epithelium in celiac disease are due 2031-02-28 (open). Because deadlines can change, verify the date with the funder, NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Cytotoxic T cells and the epithelium in celiac disease?
To apply for Cytotoxic T cells and the epithelium in celiac disease, 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 NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases.