Regulatory T cells in brown adipose tissue safeguard thermogenesis by restraining interferon-γ–producing lymphocytes

Abstract

Whereas visceral adipose tissue (VAT) primarily stores excess energy, brown adipose tissue (BAT) dissipates it in a process termed nonshivering thermogenesis. Several key VAT features, particularly murine epidydimal VAT, are regulated by a distinct population of regulatory T (T_reg) cells, raising the question of whether BAT hosts an analogous population. Although T_reg cells have been observed in BAT, their properties and mechanisms of action require elucidation. We found BAT T_reg cells to be heterogeneous in subtissular localization and subtype composition. Punctual depletion of T_reg cells unleashed interferon-γ (IFN-γ)–producing lymphocytes in BAT, but not in subcutaneous or visceral fat depots, leading to IFN-γ–dependent mitochondrial dysfunction and metabolic dysregulation, thereby impeding nonshivering thermogenesis. Cold challenge selectively expanded the IL-18R1⁺ T_reg subtype in BAT; stripping this receptor specifically from T_reg cells unleashed IFN-γ–producing lymphocytes and compromised temperature control. Thus, control of local IFN-γ production is a core feature of T_reg cell control of tissue homeostasis.