STE20 kinase TAOK3 regulates type 2 immunity and metabolism in obesity.

Healthy adipose tissue (AT) contains ST2+ Tregs, ILC2s, and alternatively activated macrophages that are lost in mice or humans on high caloric diet. Understanding how this form of type 2 immunity is regulated could improve treatment of obesity. The STE20 kinase Thousand And One amino acid Kinase-3 (TAOK3) has been linked to obesity in mice and humans, but its precise function is unknown. We found that ST2+ Tregs are upregulated in visceral epididymal white AT (eWAT) of Taok3-/- mice, dependent on IL-33 and the kinase activity of TAOK3. Upon high fat diet feeding, metabolic dysfunction was attenuated in Taok3-/- mice. ST2+ Tregs disappeared from eWAT in obese wild-type mice, but this was not the case in Taok3-/- mice. Mechanistically, AT Taok3-/- Tregs were intrinsically more responsive to IL-33, through higher expression of ST2, and expressed more PPARγ and type 2 cytokines. Thus, TAOK3 inhibits adipose tissue Tregs and regulates immunometabolism under excessive caloric intake. © 2023 Maes et al.

Citation

Bastiaan Maes, Farzaneh Fayazpour, Leen Catrysse, Guillaume Lornet, Evelien Van De Velde, Caroline De Wolf, Sofie De Prijck, Justine Van Moorleghem, Manon Vanheerswynghels, Kim Deswarte, Benedicte Descamps, Christian Vanhove, Bart Van der Schueren, Roman Vangoitsenhoven, Hamida Hammad, Sophie Janssens, Bart N Lambrecht. STE20 kinase TAOK3 regulates type 2 immunity and metabolism in obesity. The Journal of experimental medicine. 2023 Sep 04;220(9)

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PMID: 37347461

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