Destabilization of renal regulatory T cells in a preclinical model of hypertension 3355

Abstract Description Hypertension is a disease of chronic, dysregulated inflammation. Emerging evidence suggest that CD4+ T cells skew towards pro-inflammatory subsets during hypertension. Regulatory T cells (Tregs) are a subset that promote peripheral tolerance and limit inflammation. Thus, Tregs are considered protective against hypertension, particularly at sites of associated organ injury such as the kidney. Tregs are primarily identified by their expression of lineage-specifying transcription factor Foxp3. Recent evidence in autoimmune models demonstrate that Tregs can become unstable and turn into “exTregs” with loss of Foxp3 expression and gain of pro-inflammatory effector function. Yet, most studies on the role of Tregs in hypertension are limited by their reliance on Foxp3 expression status. Using the Treg lineage-tracing mouse model Foxp3CreGFPRosaLSL-TdTomato, we demonstrate that mice with Angiotensin II (Ang II)-induced hypertension have increased frequency of exTregs in their kidneys. In contrast, increases in exTregs were not observed in other hypertension-related organs such as the aorta. Hypertensive mice also have less total renal Foxp3+ Tregs, with an increase in exTreg/Foxp3+ Treg ratio. In line with these findings, kidneys of Ang II-induced mice also have higher levels of pro-inflammatory cytokines such as TNFα. Together, our data suggest that Tregs can become dysfunctional during hypertension and may contribute to hypertensive pathophysiology via increased renal inflammation. Funding Sources Supported by F31HL176154, 23IPA1054281 Topic Categories Basic Autoimmunity (BA)