Transcriptional and functional identity of human t follicular helper cells across tissues
Active Project Grant Awarded Last action
- Award ID
- R21AI194144
- Recipient
-
The Trustees Of Columbia University In The City Of New York UEI QHF5ZZ114M72
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $452,375
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date 60% complete
- Place of performance
- New York, NY 10032, USA
Award details come from USAspending.gov.
Description
- Abstract
- T follicular helper cells (TFH) are indispensable for the development of memory b cells and plasma cells, facilitating protective antibody responses through a mechanism known as b cell help. The expression of lineage-defining molecules like BCL6 and CXCR5 enables TFH cells to migrate to b cell zones of lymphoid follicles, where they provide this essential support. However, examination of TFH cells in humans is challenging due to their obligate tissue localization. Additionally, t cells with TFH-like functions, known as peripheral helper t cells (TPH), have been identified in non-lymphoid tissues of mice where they mediate localized b cell responses to provide protection against reinfection. In humans, studies of TPH cells have been limited to samples isolated from autoimmune and chronic inflammatory conditions, where they are implicated in pathology, and IT is unclear whether these cells can also play protective roles in healthy mucosal sites in humans. A systematic analysis of human TFH cells across lymphoid and mucosal tissues is crucial for defining how t cells influence tissue-specific humoral immunity during infection, autoimmunity, and vaccine responses. In the proposed study, we will make use of our novel human tissue resource, from which we have unparalleled access to multiple mucosal and lymphoid tissues from adult and pediatric organ donors. Preliminary analysis of these samples reveals an enrichment of TFH and TFH-like populations across mucosal and lymphoid sites of children, necessitating examination in early life to define these populations, their properties, and functionality across different sites. In preliminary studies, we identified TFH-like cells in the lung, which express certain phenotypes of TFH cells and produced IL-21 associated with TFH functional responses. Lung TFH-like cells also express site-specific signatures including production of multiple effector cytokines while also sharing a set of core genes with TFH that are associated with b cell help. We hypothesize that human TFH cells possess a set of core features across diverse lymphoid and mucosal tissues, but exhibit functional adaptations specific to the site in which they reside. We will address this hypothesis in two aims: (1) identify a core signature and site- specific adaptations of TFH cells across diverse human tissues, (2) determine role of site-specific TFH cell functions in b cell differentiation. We will dissect the transcriptional mechanisms that specifically, or synergistically, regulate TFH differentiation, functionality and localization, while interrogating the molecular machinery underlying functional responses for promoting b cell differentiation and antibody secreting cells by TFH cells isolated from different tissues. This innovative and exploratory study aims to elucidate the cellular and molecular mechanisms behind the essential function of b cell help in various human tissue sites. Understanding these mechanisms could pave the way for tissue targeted approaches that induce localized immune responses after vaccination or dampen these responses in autoimmune conditions, all while preserving the overall integrity of the immune system.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $205,625 | |
| Original award | $246,750 |
Quick answers
Who received award R21AI194144?
R21AI194144 was awarded to The Trustees Of Columbia University In The City Of New York by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on August 1, 2025.
How much is award R21AI194144 worth?
$452,375 has been obligated on R21AI194144.
On GovTribe
See this award's full record
- Every transaction and subaward
- The recipient's other awards and teaming partners
- Similar grant awards
- Ask GovTribe AI about this award