Environmental factors underlying divergent AHR-mediated CD4+ t cell differentiation
Active Project Grant Awarded Last action
- Award ID
- F31AI194559
- Recipient
-
University Of California, Davis UEI TX2DAGQPENZ5
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $87,498
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date 0% complete
- Place of performance
- Davis, CA, USA
Award details come from USAspending.gov.
Description
- Abstract
- Environmental factors play pivotal roles in the balance between human health and disease. One environmental sensor implicated in disease is the aryl hydrocarbon receptor (AHR), a transcription factor that is activated in response to environmental signals. AHR is expressed in immune cells and is activated by diverse ligands exhibiting the capacity to integrate various environmental cues into molecular responses. AHR ligands include 2,3,7,8-tetrachlorodibenzo-p-dioxin (tcdd), an environmental pollutant, diet-derived metabolites in cruciferous vegetables (e.g. indole-3-carbinol), and microbiota-derived tryptophan metabolites. Our laboratory previously found that systemic activation of AHR by tcdd increases immunosuppressive CD4+ t regulatory cells and prevents the development of type 1 diabetes (T1D) in nonobese diabetic (NOD) mice. In contrast, dietary indole- 3-carbinol activates AHR in the intestine, increases a subset of proinflammatory CD4+ t-helper 17 cells, shifts the GUT microbiome, and promotes T1D in NOD mice. These contradictory data led US to the question: how does activation of the same receptor promote divergent CD4+ t cell subsets and T1D phenotypes? Our central hypothesis is that AHR-microbiome interactions influence the outcome of CD4+ t cell differentiation. To test this hypothesis, we will analyze CD4+ t cell differentiation following tcdd and indole-3-carbinol exposures in three different NOD mouse models: 1) transgenic mice with islet antigen-specific CD4+ t cells, 2) AHR knockout mice, and 3) gnotobiotic mice. I will determine if AHR signaling is required within t cells for their differentiation and how the microbiome influences t cell differentiation upon AHR ligand exposures. Ultimately, the data will help elucidate environmental determinants of autoimmune disease.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $43,749 | |
| Amendment | $43,749 | |
| Original award | $0 |
Quick answers
Who received award F31AI194559?
F31AI194559 was awarded to University Of California, Davis by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on November 21, 2026.
How much is award F31AI194559 worth?
$87,498 has been obligated on F31AI194559.
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