Role of S1PRS and KLF transcription factors in CD8T cell trafficking
Active Project Grant Awarded Last action
- Award ID
- F31AI188630
- Recipient
-
Regents Of The University Of Minnesota UEI KABJZBBJ4B54
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $253,891
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date 88% complete
- Place of performance
- Minneapolis, MN 55455, USA
Award details come from USAspending.gov.
Description
- Abstract
- CD8+ t cells are pivotal players in the adaptive immune response, undergoing dynamic functional transitions crucial for mounting effective responses to antigens. Upon encountering pathogens, CD8+ t cells differentiate into effector cells responsible for pathogen clearance and memory t cells providing long-term protection against reinfections. Concurrently, migratory patterns of CD8+ t cells change with differentiation, where naïve t cells recirculate, effector and circulating memory t cells (tcircm) distribute into various tissues, and resident memory t cells (TRM) become localized long-term in tissues. Krüppel-like factor 2 (KLF2) emerges as a critical regulator of t cell trafficking, particularly through its control of sphingosine-1-phosphate receptor 1 (S1PR1) expression. While expression of KLF2 or S1PR1 inhibits TRM formation, its role in regulating other aspects of t cell trafficking remains incompletely understood. Additionally, IT is unclear whether KLF2 maintains memory t cell trafficking patterns beyond initial differentiation. This study aims to address these gaps by elucidating the mechanisms of S1PR1-independent KLF2-regulated CD8+ t cell trafficking and differentiation (aim 1). Leveraging genetic manipulation and gene expression analysis, we will explore redundancy among S1PR factors and investigate non-S1PR molecules in effector and memory t cell trafficking. Furthermore, we will uncouple t cell trafficking from KLF2 expression to assess its influence on differentiation. In aim 2, we will evaluate the role of KLF2 in reinforcing memory t cell recirculation versus tissue residency. Through inducible gene expression/deletion models, we will determine how KLF2 modulation affects TRM and tcircm migration characteristics post-establishment of memory. This investigation holds therapeutic implications for manipulating memory t cell localization, crucial in combating pathogens and tumors while resisting exhaustion. Overall, this comprehensive study will deepen our understanding of KLF2's multifaceted role in CD8+ t cell trafficking and function, offering insights into potential therapeutic strategies for immune modulation in various disease contexts.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $576 | |
| Amendment | $36,349 | |
| Amendment | $36,349 | |
| Amendment | $564 | |
| Amendment | $564 | |
| Amendment | $564 | |
| Amendment | $35,785 | |
| Amendment | $0 | |
| Amendment | $35,785 | |
| Amendment | $35,785 | |
| Amendment | $0 | |
| Amendment | $35,785 | |
| Amendment | $0 | |
| Amendment | $35,785 | |
| Original award | $0 |
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Quick answers
Who received award F31AI188630?
F31AI188630 was awarded to Regents Of The University Of Minnesota by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on June 26, 2025.
How much is award F31AI188630 worth?
$253,891 has been obligated on F31AI188630.
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