Foxo in T Cells Regulates Thermogenic Program through Ccr4/Ccl22 Axis.

Area of Science:

• Immunology
• Metabolism
• Endocrinology

Background:

• Immune system and thermogenic processes are interconnected, influencing metabolic energy regulation.
• Forkhead box (Foxo) transcription factors play roles in cellular metabolism and immune responses.

Purpose of the Study:

• To investigate the role of Foxo transcription factors in CD4+ T-cells on metabolic regulation.
• To explore the impact of modulating Foxo in T-cells on energy expenditure and obesity under high-fat diet conditions.

Main Methods:

• Generation of thermogenic program-accelerating mice (T-QKO) with Foxo1 knockout and Foxo3 hetero-knockout in CD4+ T-cells.
• Assessment of metabolic phenotypes, energy expenditure, and gene expression in adipose tissue following high-fat diet and cold exposure.

Main Results:

• T-QKO mice exhibited a lean phenotype and increased energy expenditure under high-fat diet.
• Cold exposure upregulated thermogenic genes (Ppargc1a, Ucp1), Th2 cytokines (Il4, Il13), and Gata3 in subcutaneous adipose tissue.
• Cold exposure increased Ccr4 in T-cells and Ccl22 in adipose tissue, leading to Th2 cell accumulation and beige adipocyte formation.

Conclusions:

• Cold exposure recruits Th2 cells to subcutaneous adipose tissue via a Foxo-dependent pathway, regulating energy expenditure.
• Inhibiting Foxo in T-cells presents a potential therapeutic strategy for obesity treatment.