In:
Journal of Experimental Medicine, Rockefeller University Press, Vol. 220, No. 9 ( 2023-09-04)
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0022-1007
,
1540-9538
DOI:
10.1084/jem.20210788
Language:
English
Publisher:
Rockefeller University Press
Publication Date:
2023
detail.hit.zdb_id:
1477240-1
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