ICOS signaling limits regulatory T cell accumulation and function in visceral adipose tissue
| Autor: | Erika T Hayes, Kristen Mittelsteadt, Daniel J. Campbell |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Regulatory T cell T cell Immunology Population Adipose tissue Autoimmunity Intra-Abdominal Fat Diet High-Fat T-Lymphocytes Regulatory Article Inducible T-Cell Co-Stimulator Protein Mice Phosphatidylinositol 3-Kinases 03 medical and health sciences 0302 clinical medicine medicine Animals Insulin Immunology and Allergy Obesity education PI3K/AKT/mTOR pathway Inflammation education.field_of_study Phosphoinositide 3-kinase biology nutritional and metabolic diseases FOXP3 Forkhead Transcription Factors Cell biology Metabolism 030104 developmental biology medicine.anatomical_structure Adipose Tissue biology.protein Female Insulin Resistance Signal transduction human activities tissues Signal Transduction 030215 immunology |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.20201142 |
| Popis: | The authors demonstrate that loss of ICOS-dependent PI3-kinase signaling supports visceral adipose tissue (VAT) TR abundance and function, and correlates with reduced adipose inflammation and improved insulin sensitivity after a high-fat diet. This highlights a new pathway regulating VAT-TR activity. A unique population of Foxp3+ regulatory T cells (TRs) resides in visceral adipose tissue (VAT) that regulates adipose inflammation and helps preserve insulin sensitivity. Inducible T cell co-stimulator (ICOS) is highly expressed on effector (e)TRs that migrate to nonlymphoid tissues, and contributes to their maintenance and function in models of autoimmunity. In this study, we report an unexpected cell-intrinsic role for ICOS expression and downstream phosphoinositide 3-kinase (PI3K) signaling in limiting the abundance, VAT-associated phenotype, and function of TRs specifically in VAT. Icos−/− mice and mice expressing a knock-in form of ICOS that cannot activate PI3K had increased VAT-TR abundance and elevated expression of canonical VAT-TR markers. Loss of ICOS signaling facilitated enhanced accumulation of TRs to VAT associated with elevated CCR3 expression, and resulted in reduced adipose inflammation and heightened insulin sensitivity in the context of a high-fat diet. Thus, we have uncovered a new and surprising molecular pathway that regulates VAT-TR accumulation and function. Graphical Abstract |
| Databáze: | OpenAIRE |
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