TY - JOUR
T1 - STE20 kinase TAOK3 regulates type 2 immunity and metabolism in obesity
AU - Maes, Bastiaan
AU - Fayazpour, Farzaneh
AU - Catrysse, Leen
AU - Lornet, Guillaume
AU - Van De Velde, Evelien
AU - De Wolf, Caroline
AU - De Prijck, Sofie
AU - Van Moorleghem, Justine
AU - Vanheerswynghels, Manon
AU - Deswarte, Kim
AU - Descamps, Benedicte
AU - Vanhove, Christian
AU - Van der Schueren, Bart
AU - Vangoitsenhoven, Roman
AU - Hammad, Hamida
AU - Janssens, Sophie
AU - Lambrecht, Bart N.
N1 - Publisher Copyright: © 2023 Maes et al.
PY - 2023/9/4
Y1 - 2023/9/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85164041431&partnerID=8YFLogxK
U2 - 10.1084/jem.20210788
DO - 10.1084/jem.20210788
M3 - Article
C2 - 37347461
AN - SCOPUS:85164041431
SN - 0022-1007
VL - 220
JO - The Journal of experimental medicine
JF - The Journal of experimental medicine
IS - 9
M1 - e20210788
ER -
