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| Item Type: | Article |
|---|---|
| Title: | Aryl hydrocarbon receptor activation promotes effector CD4(+) T cell homeostasis and restrains salt-sensitive hypertension |
| Creators Name: | Molina, P.A., Edell, C.J., Dunaway, L.S., Kellum, C.E., Muir, R.Q., Jennings, M.S., Colson, J.C., De Miguel, C., Rhoads, M.K., Buzzelli, A.A., Harrington, L.E., Meza-Perez, S., Randall, T.D., Botta, D., Müller, D.N., Pollock, D.M., Maynard, C.L. and Pollock, J.S. |
| Abstract: | Excess dietary salt and salt-sensitivity contribute to cardiovascular disease. Distinct T cell phenotypic responses to high salt and hypertension as well as influences from environmental cues are not well understood. The aryl hydrocarbon receptor (AhR) is activated by dietary ligands, promoting T cell and systemic homeostasis. We hypothesized that activating AhR supports CD4(+) homeostatic functions, such as cytokine production and mobilization, in response to high salt intake while mitigating salt-sensitive hypertension. In the intestinal mucosa, we demonstrate that a high salt diet (HSD) is a key driving factor, independent of hypertension, in diminishing interleukin 17A (IL-17A) production by CD4(+) T (Th17) cells without disrupting circulating cytokines associated with Th17 function. Previous studies suggest that hypertensive patients and individuals on a high salt diet are deficient in AhR ligands or agonistic metabolites. We found that activating AhR augments Th17 cells during experimental saltsensitive hypertension. Further, we demonstrate that activating AhR in vitro contributes to sustaining Th17 cells in the setting of excess salt. Using photoconvertible Kikume GreenRed mice, we also revealed that HSD drives CD4(+) T cell mobilization. Next, we found that excess salt augments T cell mobilization markers, validating HSD-driven T cell migration. Also, we found that activating AhR mitigates HSD-induced T cell migration markers. Using telemetry in a model of experimental salt-sensitivity, we found that activating AhR prevents the development of salt-sensitive hypertension. Collectively, stimulating AhR through dietary ligands facilitates immunologic and systemic functions amid excess salt intake and restrains the development of salt-sensitive hypertension. |
| Keywords: | Aryl Hydrocarbon Receptor, Th17, High Salt Diet, Salt-Sensitive Hypertension, Blood Pressure, Animals, Mice |
| Source: | Function |
| ISSN: | 2633-8823 |
| Publisher: | Oxford University Press |
| Page Range: | zqaf001 |
| Date: | 8 January 2025 |
| Official Publication: | https://doi.org/10.1093/function/zqaf001 |
| PubMed: | View item in PubMed |
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