Metabolic control in VAT by Tregs through OSM-mediated suppression of adipogenesis
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ABSTRACT: Regulatory T cells (Tregs) play diverse roles in tissue homeostasis. In visceral adipose tissue (VAT), resident Tregs, enriched with PPARγ, are clonally expanded in a IL-33 dependent manner. However, the tissue-specific functions of VAT Tregs, with unique transcriptome compared to spleen or other peripheral tissues, remain largely unknown. We identified two PPARγ+ mesenchymal stromal cells in VAT (VmSCs), named VmSC4s (PPARγ+Thy1-) and 5s (PPARγ+Thy1+). Lineage-tracing and transcriptome analysis revealled that VmSC4s contain precursors for VmSC5s. We also demonstrated that VAT Tregs directly suppress adipogenic differentation of VmSC5s through Oncostain M (OSM) to promote insulin sensitivity and glucose tolerance. Thus, VAT-Treg-derived OSM and VmSCs-displayed OSMR maintain tissue homeostasis via limiting the differentiation of dysfunctional adipocytes, which provide therapeutic targets for treating obesity and diabetes.
ORGANISM(S): Mus musculus
PROVIDER: GSE226889 | GEO | 2023/08/01
REPOSITORIES: GEO
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