BES2021 Belgian Endocrine Society 2021 Abstracts (26 abstracts)
The STE-20 kinase TAOK3 regulates obesity-associated metabolism and type 2 immunity in murine adipose tissue
Maes Bastiaan 1,2,3,4 , Fayazpour Farzaneh 2,3 , Catrysse Leen 5,6 , Lornet Guillaume 1 , Van De Velde Evelien 2,3 , De Wolf Caroline 1,2 , De Prijck Sofie 1,2 , Van Moorleghem Justine 1,2 , Vanheerswynghels Manon 1,2 , Deswarte Kim 1,2 , Descamps Benedicte 7 , Vanhove Christian 7 , Hammad Hamida 1,2 , Janssens Sophie 1,2,3,* & Lambrecht Bart N 1,2,9,*
1Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent 9052, Belgium; 2Department of Internal Medicine and Pediatrics, Ghent University, Ghent 9000, Belgium; 3Laboratory for Endoplasmic Reticulum Stress and Inflammation, VIB-UGent Center for Inflammation Research, Ghent 9052, Belgium; 4Department of Endocrinology, Ghent University Hospital, Ghent 9000, Belgium; 5Cellular and Molecular (Patho)Physiology, VIB-UGent Center for Inflammation Research, Ghent 9000, Belgium; 6Department of Biomedical Molecular Biology, Ghent University, Ghent 9000, Belgium; 7IBiTech-MEDISIP-Infinity Lab, Department of Electronics and Information Systems, Ghent University, Ghent 9000, Belgium; 8Department of Endocrinology, Ghent University Hospital, Ghent 9000, Belgium; 9Department of Pulmonary Medicine, Erasmus University Medical Center Rotterdam, Rotterdam 3015 GJ, the Netherlands;*These authors shared supervision of the work
Aim: Healthy adipose tissue contains numerous innate and adaptive immune cells that carry a type 2 cytokine immune signature, controlled by IL-33 and reflected by accumulation of ST2+ T regulatory cells (Tregs), type 2 innate lymphoid cells (ILC2s), and alternatively activated macrophages. These type 2 responses are lost in mice or humans on high-caloric diets that lead to obesity. Understanding how type 2 immunity is regulated in adipose tissue could contribute to prevention and treatment of obesity. The STE-20 kinase Thousand and one amino acid kinase-3 (TAOK3) has been linked to immune regulation and obesity in mice and humans, but its precise function is unknown.
Methodology: We used whole-body Taok3-/- mice on a C57BL/6J background. Organs were harvested from 12 week old mice for processing to single cell suspensions, and then stained with fluorochrome labeled antibodies. Samples were analyzed on a BD LSRFortessaTM. Next, mice were fed a high-fat diet (60% fat) for 15 weeks. Metabolic homeostasis was analyzed by performing intra-peritoneal glucose tolerance challenge and insulin tolerance challenge. Tissues were taken and analyzed as above. Gene expression was analyzed from RNA isolated from flow cytometry sorted Tregs.
Results: Here, we show that ST2-expressing Tregs are upregulated in diverse tissues of Taok3-/- mice, but particularly in epididymal visceral white adipose tissue (eWAT) of male Taok3-/- mice. Whereas ST2+ Tregs disappeared from eWAT upon high-fat diet in wild-type mice, they were spared in obese Taok3-/- eWAT. Concomitantly, diet-induced metabolic dysfunction was attenuated in Taok3-/- mice. Mechanistically, adipose tissue Taok3-/- Tregs were more responsive to IL-33, through higher expression of ST2, and expressed more PPAR and type 2 cytokines.
Conclusion: Taken together, Taok3 regulates the homeostasis of ST2+ Tregs in adipose tissue and contributes to metabolic dysfunction upon excessive caloric intake. Inhibiting Taok3 kinase activity might prove to be an interesting route in targeting immune dysregulation associated with obesity.
Volume 79
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