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

Group 2 innate lymphoid cells (ILC2s) represent the major player during hyperresponsive airway inflammation. Peroxisome proliferator-activated receptor-gamma (PPAR gamma) was highly expressed on ILC2 and its potential role in asthma has been suggested. However, the detailed mechanism underlying the effects of PPAR gamma on ILC2-induced airway inflammation remains to be fully understood. Here we identified PPAR gamma as a positive regulator of lung ILC2. Expression of PPAR gamma on ILC2 was dramatically induced upon interleukin-33 (IL-33) challenge. Deficiency of PPAR gamma in hematopoietic system in mice (PPAR gamma(fl/fl)Vav1(Cre)) 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 PPAR gamma(fl/fl)littermates control. Mechanistic studies identified IL-33 receptor ST2 as a transcriptional target of PPAR gamma. Overexpression of ST2 rescued the functional defects of ILC2 lacking PPAR gamma. Collectively, these results demonstrated PPAR gamma as an important regulator of ILC2 during allergic airway inflammation, which sheds new lights on the importance of PPAR gamma in asthma.

Automated summary

The study identified PPARγ as a positive regulator of ILC2 in allergic airway inflammation through modulation of the ST2 receptor. Deficiency of PPARγ significantly alleviated the function of ILC2 and reduced symptoms of airway inflammation.