| Title: |
Regulatory T cells in brown adipose tissue safeguard thermogenesis by restraining interferon-γ–producing lymphocytes. |
| Authors: |
Zammit, Nathan W.; Vargas-Castillo, Ariana; Langston, P. Kent; Wang, Gang; Zhou, Yangzhong; Spiegelman, Bruce M.; Benoist, Christophe; Mathis, Diane |
| Source: |
Science Immunology; 2025, Vol. 10 Issue 109, p1-16, 16p |
| Subject Terms: |
Regulatory T cells; Brown adipose tissue; Body temperature regulation; Interferon gamma; Mitochondrial pathology; Metabolic disorders; Caloric expenditure |
| 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 (Treg) cells, raising the question of whether BAT hosts an analogous population. Although Treg cells have been observed in BAT, their properties and mechanisms of action require elucidation. We found BAT Treg cells to be heterogeneous in subtissular localization and subtype composition. Punctual depletion of Treg 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+ Treg subtype in BAT; stripping this receptor specifically from Treg cells unleashed IFN-γ–producing lymphocytes and compromised temperature control. Thus, control of local IFN-γ production is a core feature of Treg cell control of tissue homeostasis. Editor's summary: Brown adipose tissue (BAT) generates heat by dissipating stored energy through the process of thermogenesis. Regulatory T (Treg) cells support visceral adipose tissue (VAT) metabolic health, but whether and how Treg cells support BAT homeostasis remains unclear. Zammit et al. found in mice that BAT harbors a distinct population of Treg cells that protects brown adipocytes from interferon-γ (IFN-γ)–driven mitochondrial dysfunction. Acute loss of Treg cells increased IFN-γ production by local lymphocytes, leading to impaired energy expenditure and cold tolerance. These results identify a role for Treg cells in supporting BAT function and highlight their broader role in preserving tissue homeostasis by locally restraining IFN-γ–producing lymphocytes. —Claire Olingy [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |