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Foxo in T Cells Regulates Thermogenic Program through Ccr4/Ccl22 Axis
- Source :
- iScience, iScience, Vol 22, Iss, Pp 81-96 (2019)
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Summary Crosstalk between immunity and the thermogenic program has provided insight into metabolic energy regulation. Here, we generated thermogenic program-accelerating mice (T-QKO), in which Foxo1 is knockout and Foxo3 is hetero-knockout in CD4+ T cells. T-QKO exhibit lean phenotype under HFD due to increased energy expenditure. Cold exposure significantly increased expression of the thermogenic genes (Ppargc1a and Ucp1), Th2 cytokines (Il4 and Il13), and Th2 marker gene (Gata3) in subcutaneous adipose tissue (SC) of T-QKO. Furthermore, Ccr4 expression was significantly increased in Th2 cells of T-QKO, and cold exposure induced Ccl22 expression in SC, leading to increased accumulation of Th2 cell population in SC of T-QKO. These data reveal a mechanism by which cold exposure induces selective recruitment of Th2 cells into SC, leading to regulation of energy expenditure by generating beige adipocyte and suggest that inhibition of Foxo in T cells may support a strategy to prevent and treat obesity.<br />Graphical Abstract<br />Highlights • T-QKO increases Gata3 and Ccr4 expression in CD4+ T cells • Cold exposure increases Ccl22 expression in subcutaneous adipose tissue • Cold exposure increases SC-specific recruitment of Th2 cells in T-QKO • Recruited Th2 cells secrete IL-4 and IL-13 and increase beiging of adipocytes<br />Molecular Mechanism of Behavior; Immunology; Immune Response; Diabetology
- Subjects :
- 0301 basic medicine
Immunology
Cell
Population
FOXO1
02 engineering and technology
Article
03 medical and health sciences
Immune system
medicine
lcsh:Science
education
Immune Response
Interleukin 4
education.field_of_study
Multidisciplinary
Chemistry
GATA3
Diabetology
021001 nanoscience & nanotechnology
Cell biology
030104 developmental biology
medicine.anatomical_structure
FOXO3
lcsh:Q
Molecular Mechanism of Behavior
PPARGC1A
0210 nano-technology
Subjects
Details
- ISSN :
- 25890042
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- iScience
- Accession number :
- edsair.doi.dedup.....dff8b4cedc6ae1c9f63a27bbc793c3bd