Immunometabolic switch in hypertension: how dendritic cell mineralocorticoid receptors drive Th17 polarization and blood pressure control

Graphical AbstractThe dendritic cell mineralocorticoid receptor controls blood pressure by regulating Th17 polarization and differentiation. The MR in DCs negatively regulates the expression of Plcβ1 and Plcβ4. In general, Plcβ1 forms a complex with SHP-1 and Stat5. Then, SHP-1 dephosphorylates phospho-Stat5 to deactivate this form, which then negatively regulates immune signalling. The Plcβ1/Plcβ4–Stat5–NF-κB pathway plays a crucial role in DC activation and Th17 differentiation. Thus, the DC MR controls blood pressure and enhances target organ damage by the regulation of Th17 cells. Detailed descriptions are given in the text. This figure has been created with Biorender.com. Ang II, angiotensin II; BP, blood pressure; DC, dendritic cell; IL-17A, interleukin-17A; MHC II, major histocompatibility complex class II; MR, mineralocorticoid receptor; MRA, MR antagonist; NF-κB, nuclear factor kappa B; PLCβ1, phospholipase C beta 1; PLCβ4, phospholipase C beta 4; SHP-1, Src homology region 2 domain-containing phosphatase-1; Stat5, signal transducer and activator of transcription 5; TCR, T-cell receptor; Th17, T helper 17 cells; Treg, T-regulatory cell.Open in new tabDownload slide