Angiotensin II induces TSLP via an AT1 receptor/NF-KappaB pathway, promoting Th17 differentiation

Abstract

Background: Adaptive immunity plays a critical role in atherosclerosis and hypertension. T helper 17 (Th17) cells, as a new T-cell lineage, are involved in cardiovascular diseases. Dendritic cells (DCs) are the professional antigen-presenting cells with the pivotal role in orchestrating adaptive immunity. Thymic stromal lymphopoietin (TSLP) can activate DCs and trigger adaptive immune responses. What the role of TSLP in atherosclerosis and hypertension has not been investigated.

Methods and results: We measured the expression of TSLP in primary rat vascular smooth muscle cells (VSMCs) exposed to angiotensin II (Ang II) and evaluated the capacity of TSLP induced by Ang II to induce the differentiation of Th17 Cells. We then sought to identify the involved upstream regulatory mechanisms. We found that VSMCs express TSLP in response to Ang II in an AT1 receptor/NF-KappaB manner. TSLP can induce the differentiation of Th17 Cells by triggering DCs.

Conclusion: Through DC activation, Ang II-induced TSLP enhances Th17-driven immune response in atherosclerosis and hypertension.