PD-L1 reverse signaling in liver homeostasis and disease
Active Project Grant Awarded Last action
- Award ID
- R01AI186275
- Recipient
-
The Regents Of The University Of Colorado UEI MW8JHK6ZYEX8 Part of The Regents Of The University Of Colorado
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $7,344,123
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date 48% complete
- Place of performance
- Aurora, CO 80045, USA
Award details come from USAspending.gov.
Description
- Abstract
- The goal of this proposal is to identify the mechanism(s) by which programmed death ligand 1 (PD-L1) reverse or intracellular signaling acts as an immune regulator in the liver during both acute infection, chronic infection and chronic disease. Our studies have outlined a major role for PD-L1 reverse signaling in the control of dendritic cell (DC) migration, DC activation and in regulating t cell cytokine production. These findings are consistent with PD-L1 acting to mitigate type 1 interferon (IFN) signaling events. Using a murine model where just three amino acids in the cytoplasmic domain of PD-L1 are mutated to alanine, to limit reverse signaling, we find increased fibrosis in a murine model of metabolic dysfunction-associated steatohepatitis (mash) and decreased liver pathology in an acute systemic listeria infection model. Therefore, in this proposal we aim to better understand the different functions of PD-L1 reverse signaling (IE, DC migration VS activation) and how they contribute to t cell programming in listeria infection and mash. We also aim to better understand which PD-L1 expressing cells in the liver contribute to effector t cell responses and liver fibrosis in the absence of PD-L1 reverse signaling using a murine model of mash. Finally, we aim to address the importance of PD-L1 reverse signaling in the liver in the setting of acute versus chronic infection of lcmv. Together these aims will define how a widely targeted immune regulatory molecule, PD-L1, functions in the liver through intracellular signaling events not previously recognized or appreciated.
Transactions
| Action | Obligated | Date |
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| Amendment | $78,923 | |
| Amendment | $582,734 | |
| Amendment | $78,923 | |
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| Amendment | $582,734 | |
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| Amendment | $582,734 | |
| Amendment | $28,803 | |
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| Amendment | $58,272 | |
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| Amendment | $524,462 | |
| Amendment | $524,462 | |
| Amendment | $524,462 | |
| Amendment | $524,462 | |
| Amendment | $524,462 | |
| Original award | $524,462 |
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Quick answers
Who received award R01AI186275?
R01AI186275 was awarded to The Regents Of The University Of Colorado by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on June 1, 2024.
How much is award R01AI186275 worth?
$7,344,123 has been obligated on R01AI186275.
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