Abstract P143: Salt-sensitivity And Salt-resistance Differentially Modulate Renal And Colonic T Regulatory Cells

Autor: Claudia Edell, Rachel Q Muir, Jackson Colson, Patrick Molina, Jennifer S. Pollock, Craig L. Maynard
Rok vydání: 2020
Předmět:
Zdroj: Hypertension. 76
ISSN: 1524-4563
0194-911X
Popis: High salt diets (HSD) promote both inflammation and immunosuppression as shown in numerous studies utilizing salt-sensitive or hypertensive models. However, mechanisms involved in the homeostatic immune response to HSD, alone, have not been fully elucidated. Regulatory T cells (FOXP3 + CD4 + T cells) play a role in host protection against disease or environmental stressors. Further, recent studies show that RORt + expression by Tregs may represent a functional adaptation by Tregs in response to alterations to the diet. Thus, we hypothesized that these Treg populations may expand in response to HSD alone, and a hypertensive insult prior to the HSD blunts this response. We designed experiments to determine whether Tregs and RORt + Tregs expand in response to HSD or with LNAME hypertension followed by HSD. We evaluated the following groups in male C57BL/6J mice: NSD (normal salt diet, 0.4% NaCl), LNAME/NSD (0.5mg/ml for 3-wks in drinking water, followed by 3-wks NSD), HSD (4% NaCl+1% NaCl in drinking water, 2-wks), or LNAME/HSD (0.5mg/mL for 3-wks in drinking water, with 1-wk NSD followed by 2-wks HSD). Following immune cell isolation, we utilized flow cytometry to phenotype renal and colonic T cells. Data are expressed as frequency of means (% of CD4 + TCRbeta + T cells)±SEM (n=3-8/group) compared to NSD. In kidneys, HSD significantly expanded Tregs and RORt + Tregs, while LNAME/HSD group was unchanged compared to controls (% Treg: NSD: 5.7±0.5; L-NAME: 6.5±0.5; HSD: 9.2±1.0**; LNAME/HSD: 6.2±0.3; % RORt + Treg: NSD: 0.4±0.07; L-NAME: 0.6±0.13; HSD: 1.8±0.41***; LNAME/HSD: 0.6±0.14; **p+ Tregs, whereas the LNAME/HSD group had no change in these T cell populations (% Treg: NSD: 36±2; LNAME: 42±1; HSD: 46±2*; LNAME/HSD: 43±2; % RORt + Tregs: NSD: 16±1; LNAME: 19±1; HSD: 23±1*; LNAME/HSD: 20±2; *p+ Tregs expand in response to HSD in the kidney and colon, with a greater magnitude of expansion by RORt + Tregs. However, this expansion of T cell populations is not evident in mice pre-exposed to a hypertensive insult. We propose that HSD stimulates pathways that promote Treg expansion, which may be associated with salt-resistance and protective mechanisms.
Databáze: OpenAIRE
Externí odkaz: