| Autor: |
Toomer KH; Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA., Lui JB; Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA., Altman NH; Department of Pathology, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA., Ban Y; Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA., Chen X; Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA.; Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA., Malek TR; Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA. tmalek@med.miami.edu.; Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA. tmalek@med.miami.edu. |
| Abstrakt: |
IL-2R signaling is essential for regulatory T cell (Treg) function. However, the precise contribution of IL-2 during Treg thymic development, peripheral homeostasis and lineage stability remains unclear. Here we show that IL-2R signaling is required by thymic Tregs at an early step for expansion and survival, and a later step for functional maturation. Using inducible, conditional deletion of CD25 in peripheral Tregs, we also find that IL-2R signaling is indispensable for Treg homeostasis, whereas Treg lineage stability is largely IL-2-independent. CD25 knockout peripheral Tregs have increased apoptosis, oxidative stress, signs of mitochondrial dysfunction, and reduced transcription of key enzymes of lipid and cholesterol biosynthetic pathways. A divergent IL-2R transcriptional signature is noted for thymic Tregs versus peripheral Tregs. These data indicate that IL-2R signaling in the thymus and the periphery leads to distinctive effects on Treg function, while peripheral Treg survival depends on a non-conventional mechanism of metabolic regulation. |
