IL‐33 activates eosinophils of visceral adipose tissue both directly and via innate lymphoid cells

• Published in: European journal of immunology Vol. 45; no. 3; pp. 876 - 885
• Main Authors: Hashiguchi, Masaaki, Kashiwakura, Yuji, Kojima, Hidefumi, Kobayashi, Ayano, Kanno, Yumiko, Kobata, Tetsuji
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.03.2015
• Subjects: Animals; Eosinophil Major Basic Protein - genetics; Eosinophil Major Basic Protein - immunology; Eosinophils; Eosinophils - cytology; Eosinophils - immunology; Gene Expression Regulation - immunology; IL‐33; IL‐5; Immunity, Innate - physiology; Innate lymphoid cells; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - immunology; Interleukin-33; Interleukin-5 - genetics; Interleukin-5 - immunology; Interleukins - genetics; Interleukins - immunology; Intra-Abdominal Fat - cytology; Intra-Abdominal Fat - immunology; Mice; Mice, Knockout; Innate lymphoid cells; IL-5; IL-33; Eosinophils
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201444969

Eosinophils are multifunctional leukocytes involved in allergic reactions as well as adipose tissue regulation. IL‐5 is required for eosinophil survival; however, the in vivo mechanisms of eosinophil regulation are not fully understood. A tg mouse model with il5 promoter‐driven EGFP expression was established for detecting the IL‐5‐producing cells in vivo. Il5‐egfp tg mice expressed high levels of EGFP in gonadal adipose tissue (GAT) cells. EGFP+ cells in GAT were mainly group 2 innate lymphoid cells (ILCs). IL‐33 preferentially expanded EGFP+ cells and eosinophils in GAT in vivo. EGFP+ ILCs were found to upregulate prg2 mRNA expression in GAT eosinophils. These results demonstrate that ILCs activate eosinophils in GAT. The blockage of IL‐33Rα, on the other hand, did not impair EGFP+ ILC numbers but did impair eosinophil numbers in vivo. GAT eosinophils expressed IL‐33Rα and IL‐33 expanded eosinophil numbers in CD90+ cell‐depleted mice. IL‐33 was further observed to induce the expression of retnla and epx mRNA in eosinophils. These findings demonstrate that IL‐33 directly activates eosinophils in GAT, and together with our other findings described above, our findings show that IL‐33 has dual pathways via which it activates eosinophils in vivo: a direct activation pathway and a group 2 ILC‐mediated pathway.