CD28-expressing δ T cells are increased in perivascular adipose tissue of hypertensive mice and in subcutaneous adipose tissue of obese humans.

OBJECTIVES: γδ T-lymphocytes play a role in angiotensin II (AngII)-induced hypertension, vascular injury and T-cell infiltration in perivascular adipose tissue (PVAT) in mice. Mesenteric arteries of hypertensive mice and subcutaneous arteries from obese humans present similar remodeling. We hypothesized that γδ T-cell subtypes in mesenteric vessels with PVAT (MV/PVAT) from hypertensive mice and subcutaneous adipose tissue (SAT) from obese humans, who are prone to develop hypertension, would be similar. METHODS: Mice were infused with AngII for 14 days. MV/PVAT T-cells were used for single-cell RNA-sequencing (scRNA-seq). scRNA-seq data (GSE155960) of SAT CD45 + cells from three lean and three obese women were downloaded from the Gene Expression Omnibus database. RESULTS: δ T-cell subclustering identified six δ T-cell subtypes. AngII increased T-cell receptor δ variable 4 ( Trdv4 ) + γδ T-effector memory cells and Cd28high δ T EM -cells, changes confirmed by flow cytometry. δ T-cell subclustering identified nine δ T-cell subtypes in human SAT. CD28 expressing δ T-cell subclustering demonstrated similar δ T-cell subpopulations in murine MV/PVAT and human SAT. Cd28+ γδ NKT EM and Cd28high δ T EM -cells increased in MV/PVAT from hypertensive mice and CD28high δ T EM -cells in SAT from obese women compared to the lean women. CONCLUSION: Similar CD28 + δ T-cells were identified in murine MV/PVAT and human SAT. CD28 high δ T EM -cells increased in MV/PVAT in hypertensive mice and in SAT from humans with obesity, a prehypertensive condition. CD28 + δ T-lymphocytes could have a pathogenic role in human hypertension associated with obesity, and could be a potential target for therapy.

Automated Detection and Diameter Estimation for Mouse Mesenteric Artery Using Semantic Segmentation.

BACKGROUND: Pressurized myography is useful for the assessment of small artery structures and function. However, this procedure requires technical expertise for sample preparation and effort to choose an appropriate sized artery. In this study, we developed an automatic artery/vein differentiation and a size measurement system utilizing machine learning algorithms. METHODS AND RESULTS: We used 654 independent mouse mesenteric artery images for model training. The model yielded an Intersection-over-Union of 0.744 ± 0.031 and a Dice coefficient of 0.881 ± 0.016. The vessel size and lumen size calculated from the predicted vessel contours demonstrated a strong linear correlation with manually determined vessel sizes (R = 0.722 ± 0.048, p < 0.001 for vessel size and R = 0.908 ± 0.027, p < 0.001 for lumen size). Last, we assessed the relation between the vessel size before and after dissection using a pressurized myography system. We observed a strong positive correlation between the wall/lumen ratio before dissection and the lumen expansion ratio (R = 0.832, p < 0.01). Using multivariate binary logistic regression, 2 models estimating whether the vessel met the size criteria (lumen size of 160-240 µm) were generated with an area under the receiver operating characteristic curve of 0.761 for the upper limit and 0.747 for the lower limit. CONCLUSION: The U-Net-based image analysis method could streamline the experimental approach.

Role of interleukin-23/interleukin-17 axis in T-cell-mediated actions in hypertension.

Current knowledge suggests that hypertension is in part mediated by immune mechanisms. Both interleukin (IL)-23 and IL-17 are up-regulated in several experimental hypertensive rodent models, as well as in hypertensive humans in observational studies. Recent preclinical studies have shown that either IL-23 or IL-17A treatment induce blood pressure elevation. However, the IL-23/IL-17 axis has not been a major therapeutic target in hypertension, unlike in other autoimmune diseases. In this review, we summarize current knowledge on the role of these cytokines in immune mechanisms contributing to hypertension, and discuss the potential of IL-23/IL-17-targeted therapy for treatment of hypertension.