Metabolic regulation by PPARγ is required for IL-33-mediated activation of ILC2s in lung and adipose tissue.
Mucosal Immunol
; 14(3): 585-593, 2021 05.
Article
em En
| MEDLINE
| ID: mdl-33106586
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pneumonia
/
Hipersensibilidade Respiratória
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Linfócitos
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Tecido Adiposo
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PPAR gama
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Interleucina-33
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Pulmão
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article