Metabolic regulation by PPARγ is required for IL-33-mediated activation of ILC2s in lung and adipose tissue.
Adipose Tissue
/ immunology
Animals
CD36 Antigens
/ metabolism
Cells, Cultured
Cytokines
/ metabolism
Down-Regulation
Humans
Interleukin-33
/ metabolism
Lung
/ immunology
Lymphocytes
/ immunology
Mice
Mice, Inbred C57BL
Mice, Knockout
PPAR gamma
/ genetics
Pneumonia
/ immunology
Respiratory Hypersensitivity
/ immunology
Th2 Cells
/ immunology
Journal
Mucosal immunology
ISSN: 1935-3456
Titre abrégé: Mucosal Immunol
Pays: United States
ID NLM: 101299742
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
27
06
2020
accepted:
04
10
2020
revised:
23
09
2020
pubmed:
28
10
2020
medline:
21
12
2021
entrez:
27
10
2020
Statut:
ppublish
Résumé
Type 2 innate lymphoid cells (ILC2s) play a critical role early in the response to infection by helminths and in the development of allergic reactions. ILC2s are also involved in the physiologic regulation of adipose tissue and its metabolic response to cold shock. We find that the metabolic sensor peroxisome proliferator-activated receptor gamma (PPARγ) is highly expressed in ILC2s of the lung and adipose tissue and increases responsiveness to IL-33. In turn, activation of ILC2 by IL-33 leads to increased expression of PPARγ, a prerequisite for proliferation and expression of the effector cytokines IL-5 and IL-13. In contrast, pharmacological inhibition of PPARγ leads to decreased expression of CD36 and fatty acid uptake, a necessary source of energy for ILC2s and of potential ligands for PPARγ. As a consequence, treatment of mice with a PPARγ antagonist reduces the severity of an ILC2-dependent acute airway inflammation. Together, our results demonstrate the critical role of the metabolic sensor PPARγ for the functions of ILC2s.
Identifiants
pubmed: 33106586
doi: 10.1038/s41385-020-00351-w
pii: S1933-0219(22)00160-X
doi:
Substances chimiques
CD36 Antigens
0
Cytokines
0
Interleukin-33
0
PPAR gamma
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
585-593Commentaires et corrections
Type : CommentIn
Type : CommentIn
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