Eosinophils and pleural macrophages counterregulate IL-33-elicited airway inflammation via the 12/15-lipoxygenase pathway

Emi Ito ^1,2 Reika Hayashizaki ^1,2 Takuro Hosaka ^1,2 Tsuyoshi Yamane ² Jun Miyata ^2,3 Yosuke Isobe ^1,2,4* Makoto Arita ^1,2,4*

• ¹ Keio University, Minato, Tōkyō, Japan
• ² RIKEN Yokohama, Yokohama, Kanagawa, Japan
• ³ School of Medicine, Keio University, Tokyo, Japan
• ⁴ Yokohama City University, Yokohama, Kanagawa, Japan

Fatty acid metabolism plays a crucial role in regulating airway inflammation through the synthesis of lipid mediators. We have previously demonstrated that a 12/15-lipoxygenase (12/15-LOX or Alox15)-derived mediator attenuated IL-33-induced eosinophilic airway inflammation in mice. However, cellular sources of 12/15-LOX-derived mediators that control airway inflammation remain unclear. In this study, we found that eosinophils and pleural macrophages were the major 12/15-LOX-expressing cell types responsible for attenuating airway inflammation through studies conducted in several cell type-specific conditional 12/15-LOX-deficient mice. Eosinophils were the major population of 12/15-LOX-expressing cells found in inflamed lung tissue. In addition, pleural macrophages were the major population of 12/15-LOX-expressing cells in the thoracic cavity and were found to translocate into inflamed lung tissue in response to airway inflammation. These results suggest that 12/15-LOX-expressing eosinophils and pleural macrophages cooperatively attenuate IL-33-induced airway inflammation in mice.