Details

Autor(en) / Beteiligte

• Tsuzuki, Hirofumi
• Arinobu, Yojiro
• Miyawaki, Kohta
• Takaki, Ayako
• Ota, Shun‐ichiro
• Ota, Yuri
• Mitoma, Hiroki
• Akahoshi, Mitsuteru
• Mori, Yasuo
• Iwasaki, Hiromi
• Niiro, Hiroaki
• Tsukamoto, Hiroshi
• Akashi, Koichi

Titel

Functional interleukin‐33 receptors are expressed in early progenitor stages of allergy‐related granulocytes

Ist Teil von

• Immunology, 2017-01, Vol.150 (1), p.64-73

Ort / Verlag

England: Wiley Subscription Services, Inc

Erscheinungsjahr

2017

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• Summary Interleukin‐33 (IL‐33) induces T helper type 2 (Th2) cytokine production and eosinophilia independently of acquired immunity, leading to innate immunity‐mediated allergic inflammation. Allergy‐related innate myeloid cells such as eosinophils, basophils and mast cells express the IL‐33 receptor (IL‐33R), but it is still unknown how IL‐33 regulates allergic inflammation involving these cells and their progenitors. Here, we revealed that the functional IL‐33R was expressed on eosinophil progenitors (EoPs), basophil progenitors (BaPs) and mast cell progenitors (MCPs). In the presence of IL‐33, these progenitors did not expand, but produced a high amount of Th2 and pro‐inflammatory cytokines such as IL‐9, IL‐13, IL‐1β and IL‐6. The amount of cytokines produced by these progenitors was greater than that by mature cells. In vivo, IL‐33 stimulated the expansion of EoPs, but it was dependent upon the elevated serum IL‐5 that is presumably derived from type 2 innate lymphoid cells that express functional IL‐33R. These data collectively suggest that EoPs, BaPs and MCPs are not only the sources of allergy‐related granulocytes, but can also be sources of allergy‐related cytokines in IL‐33‐induced inflammation. Because such progenitors can differentiate into mature granulocytes at the site of inflammation, they are potential therapeutic targets in IL‐33‐related allergic diseases. In this study, we revealed that eosinophil progenitors (EoPs), basophil progenitors (BaPs) and mast cell progenitors (MCPs) expressed functional interleukin‐33 (IL‐33) receptor. IL‐33 induced not only eosinophilia through IL‐5‐dependent EoP expansion but also the production of T helper type 2 and pro‐inflammatory cytokines by EoPs, BaPs and MCPs. These myeloid progenitors, which are the sources of both allergy‐related granulocytes and effector cytokines, should be potential therapeutic targets in IL‐33‐related allergic diseases.