PPARγ enhances ILC2 function during allergic airway inflammation via transcription regulation of ST2.

Abstract

Group 2 innate lymphoid cells (ILC2s) represent the major player during hyperresponsive airway inflammation. Peroxisome proliferator-activated receptor-γ (PPARγ) was highly expressed on ILC2 and its potential role in asthma has been suggested. However, the detailed mechanism underlying the effects of PPARγ on ILC2-induced airway inflammation remains to be fully understood. Here we identified PPARγ as a positive regulator of lung ILC2. Expression of PPARγ on ILC2 was dramatically induced upon interleukin-33 (IL-33) challenge. Deficiency of PPARγ in hematopoietic system in mice (PPARγfl/fl Vav1Cre) significantly impaired the function of ILC2 in lung, which led to apparent alleviation of airway inflammation in response to IL-33 or Papain challenge, when compared with those in PPARγfl/fl littermates control. Mechanistic studies identified IL-33 receptor ST2 as a transcriptional target of PPARγ. Overexpression of ST2 rescued the functional defects of ILC2 lacking PPARγ. Collectively, these results demonstrated PPARγ as an important regulator of ILC2 during allergic airway inflammation, which sheds new lights on the importance of PPARγ in asthma.

• Authors: Qiang Xiao, Juan He, Aihua Lei, Haixu Xu, Lijuan Zhang, Pan Zhou, Guanmin Jiang, Jie Zhou
• Journal: Mucosal immunology (Mucosal Immunol) Vol. 14 Issue 2 Pg. 468-478 (03 2021) ISSN: 1935-3456 [Electronic] United States
• PMID: 32811992 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Il1rl1 protein, mouse
• Interleukin-1 Receptor-Like 1 Protein
• PPAR gamma

Topics

• Animals
• Asthma (immunology)
• Cells, Cultured
• Cytokines (metabolism)
• Gene Expression Regulation
• Humans
• Hypersensitivity (immunology)
• Immunity, Innate
• Inflammation (immunology)
• Interleukin-1 Receptor-Like 1 Protein (genetics, metabolism)
• Lymphocytes (immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Inbred NOD
• Mice, Knockout
• PPAR gamma (genetics, metabolism)
• Respiratory System (immunology)
• Th2 Cells (immunology)