Aryl Hydrocarbon Receptor Activation Promotes Effector CD4+ T Cell Homeostasis and Restrains Salt-Sensitive...

Area of Science:

• Immunology
• Cardiovascular Science
• Nutritional Science

Background:

• Excess dietary salt intake and salt-sensitivity are major contributors to cardiovascular disease.
• The role of T cell responses and environmental factors like the aryl hydrocarbon receptor (AhR) in high salt-induced hypertension is not fully understood.
• AhR, activated by dietary ligands, is known to promote T cell and systemic homeostasis.

Purpose of the Study:

• To investigate whether activating AhR supports CD4+ T cell homeostatic functions during high salt intake.
• To determine if AhR activation can mitigate salt-sensitive hypertension.
• To elucidate the impact of high salt diet (HSD) on T cell phenotypes and mobilization, and the role of AhR.

Main Methods:

• Analysis of T cell (Th17) cytokine production (IL-17A) in response to HSD.
• In vitro studies activating AhR in T cells under high salt conditions.
• Use of photoconvertible mice to track CD4+ T cell mobilization.
• Telemetry to measure blood pressure in a salt-sensitive hypertension model.
• Assessment of T cell mobilization markers.

Main Results:

• HSD diminished IL-17A production by Th17 cells in the intestinal mucosa, independent of hypertension.
• AhR activation augmented Th17 cells during experimental salt-sensitive hypertension and sustained Th17 cells in vitro under high salt.
• HSD promoted CD4+ T cell mobilization, while AhR activation mitigated HSD-induced T cell migration markers.
• AhR activation prevented the development of salt-sensitive hypertension in experimental models.

Conclusions:

• High salt diet significantly impacts T cell function and mobilization.
• Activating the aryl hydrocarbon receptor (AhR) through dietary ligands supports immunologic and systemic functions during excess salt intake.
• AhR stimulation restrains the development of salt-sensitive hypertension, offering a potential therapeutic target.