CD4+ differentiated T regulatory cells is modified by physical fitness and visceral adipose tissue in young adults—A cross-sectional study

Abstract

Central adiposity and poor cardiorespiratory fitness are modifiable risk factors for various diseases. This study investigated their impact on CD4+ differentiated T regulatory (Treg) cell responses. Thirty-eight young adults were classified into high cardiorespiratory fitness/low visceral adipose tissue (High V̇O2–Low VAT, n = 20) and low cardiorespiratory fitness/high VAT (Low V̇O2–High VAT, n = 18). Body composition was assessed using DXA and ultrasound, while cardiorespiratory fitness and physical activity were measured via treadmill testing and accelerometry. CD4+ cells were cultured in Treg differentiation medium with 2 ng/mL TGF-β, with or without 100 nM rapamycin or 50 nM Torin-1, for 96 h. Differentiated Treg from Low V̇O2–High VAT participants exhibited no significant changes in IL-10 or IL-6 production with rapamycin or Torin-1. Conversely, differentiated Treg from High V̇O2–Low VAT participants showed significantly lower IL-10 production with rapamycin (p < 0.001, adjusted p < 0.001) and Torin-1 (p < 0.001, adjusted p < 0.001). These findings indicate that low cardiorespiratory fitness and high VAT contribute to an altered inflammatory response, influencing peripheral blood mononuclear cell immunophenotypes and exhaustion markers. Furthermore, mTORC1 and mTORC2 inhibition modulate cytokine production, emphasizing the role of metabolic status in immune regulation.