Dendritic cell mineralocorticoid receptor controls blood pressure by regulating T helper 17 differentiation: role of the Plcβ1/4–Stat5–NF-κB pathway
Authors' conclusion
Dendritic cell MR plays important roles in the pathogenesis of hypertension by regulating Th17 through Plcβ1/4-Stat5-NF-κB signalling, and blockade of DC MR is beneficial for treating hypertension.
Study context
- Population
- Hypertensive patients (renal biopsy and peripheral blood) and Ang II-infused mice
- Comparison
- DC mineralocorticoid receptor (MR) knockout or overexpression vs control mice; MR antagonists vs untreated
- Outcome
- Role of DC MR in BP regulation and its mechanism
Methodological detailshuman samples and mouse models, knockout and overexpression mice, Ang II-induced hypertension, In vivo DC depletion or adoptive transfer, Renal biopsy and peripheral blood from hypertensive patients for immunostaining and flow cytometry, Western blotting, chromatin immunoprecipitation, co-immunoprecipitation, RNA sequencing
- Human samples and mouse models
- Knockout and overexpression mice
- Ang II-induced hypertension
- In vivo DC depletion or adoptive transfer
- Renal biopsy and peripheral blood from hypertensive patients for immunostaining and flow cytometry
- Western blotting, chromatin immunoprecipitation, co-immunoprecipitation, RNA sequencing
Main finding
As reported in the abstract
Role of DC MR in hypertension
- MR antagonists (spironolactone and finerenone) suppressed DC aggregation and activation, as well as hypertension, in HTN and mice
- Dendritic cell MR knockout (DCMRKO) vs littermate control (LC): strikingly decreased blood pressure (BPs) and attenuated target organ damage after Ang II infusion
- DC MR deficiency mitigated Ang II-induced DC activation and Th17 differentiation (flow cytometry)
- MR-deficient dendritic cells (DCs) had elevated Plcβ1 and Plcβ4; knockdown reversed the inhibitory effect of MR deficiency on DC activation and Th17 differentiation
- Adoptive transfer of MR-deficient DCs protected against Ang II-induced hypertension; Plcβ1/4 knockdown eliminated the protective effects
- MR negatively regulated Plcβ1/4, which recruited SHP-1 to inactivate Stat5, enhancing NF-κB activation and Th17 polarization
- DC MR overexpressing (DCMROV) mice had more elevated BPs and target organ damage than control mice after Ang II infusion; differences abolished in DCMROV/IL-17AKO mice
- MR antagonists decreased Th17 aggregation in HTN and mice
Original publication
Dendritic cell mineralocorticoid receptor controls blood pressure by regulating T helper 17 differentiation: role of the Plcβ1/4–Stat5–NF-κB pathway. Eur Heart J. Published 5 November 2024. doi:10.
Summarised from the published abstract; every number is checked against it