Defining the T cell state that sustains chronic allergic disease
NIAID - National Institute of Allergy and Infectious Diseases
About This Grant
Project Summary Allergic diseases persist throughout a person’s lifetime, and the mechanisms underlying maintenance of the Th2 cells that drive these diseases are poorly understood. Chronic inflammation canonically drives T cell exhaustion in chronic infection and cancer, while Th2 cells conversely persist despite chronic inflammation We recently created a single-cell transcriptomic atlas from human tissues with allergic type 2 inflammation. A conserved set of Th2 cells was identified across tissues, including an aberrant memory-like population co-expressing TCF1 and LEF1, with evidence of chronic activation. This transcriptional profile mirrors the progenitor/stem-like CD8+ T cells that have been described in cancer and chronic infection, and we hypothesized that this Th2 cell population may serve as the reservoir that perpetuates Th2 responses. We named this cell the Th2 cell multipotent progenitor (Th2-MPP). Ex vivo functional studies established that these cells couple self-renewal with terminal differentiation in Th2, TFH- like, and Treg cells. We propose that aberrant cell-cell interactions and alarmin signaling networks in allergic tissues orchestrate an epigenetic state in Th2-MPP that enables self- renewal in the face of chronic antigen burden. The specific aims of this research strategy will investigate the epigenetic mechanisms and cell- cell interactions driving human Th2-MPP maintenance (Aim 1). Moreover, we will functionally interrogate candidate pathways through the development and characterization of a mouse model of chronic type 2 pulmonary inflammation, with temporal conditional genetic ablation of putative regulators of Th2 maintenance (Aim 2). These complimentary human and mouse immunology approaches will yield fundamental insights into the chromatin states of type 2 lymphocytes in barrier tissues and signaling mechanisms that drive this profile. Concurrently, the mechanistic studies of candidate pathways in mice will establish new avenues for the development of therapeutic modalities. This study combines mechanistic mouse models and primary human tissue analyses with cutting-edge single cell bioinformatics to provide the candidate new training in key elements of translational immunology. Through support from the co-mentors and Advisory Committee, the candidate will be well-positioned to transition to independence as an investigator, with the goal of identifying new therapeutic targets for the treatment of chronic inflammatory diseases.
Grant Summary
Defining the T cell state that sustains chronic allergic disease is a NIAID - National Institute of Allergy and Infectious Diseases grant providing up to $194K for university, nonprofit, healthcare org. Applications are due 2031-03-31 (open). Check eligibility and apply with FindGrants.
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How to Apply
Up to $194K
2031-03-31
- 1Confirm your organization is eligible for Defining the T cell state that sustains chronic allergic disease 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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Defining the T cell state that sustains chronic allergic disease: Frequently Asked Questions
Who is eligible for the Defining the T cell state that sustains chronic allergic disease?
Defining the T cell state that sustains chronic allergic disease 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 Defining the T cell state that sustains chronic allergic disease provide?
Defining the T cell state that sustains chronic allergic disease provides up to $194K 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 Defining the T cell state that sustains chronic allergic disease deadline?
Applications for Defining the T cell state that sustains chronic allergic disease are due 2031-03-31 (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 Defining the T cell state that sustains chronic allergic disease?
To apply for Defining the T cell state that sustains chronic allergic 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 NIAID - National Institute of Allergy and Infectious Diseases.