17:00 - 19:00
Room: ANA Crowne Plaza “Ohtori” Room B
Evening Symposium
Chair/s:
Kristin M. Leiferman, Kiyoshi Takatsu
IL-5-producing ILC2s and eosinophils in the development of pulmonary arteriopathy
Satoshi Takaki
Department of Immune Regulation, Research Institute, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan

Interleukin(IL)-5 regulates various functions and survival of eosinophils, and in mice the maintenance of B-1 cells. Local production of IL-5 in lung is associated with eosinophil accumulation and the exacerbation of inflammatory responses whereas eosinophils can also promote the regeneration of damaged tissues. In addition to T helper type 2 (Th2) cells, group 2 innate lymphoid cells (ILC2s) rapidly produce Th2 cytokines including IL-5 in response to IL-33, IL-25 and TSLP derived from epithelial and other cells. We have generated an IL-5 reporter mouse and revealed that IL-5-producing ILC2s resides in lung and that IL-33 induces IL-5 production by ILC2s, resulting in eosinophil accumulation in lung. IL-33 is one of critical mediators in allergic reactions. In addition, accumulating evidences suggest that IL-33 is also involved in pathogenesis of several connective tissue diseases, in which pulmonary arterial hypertension (PAH) is known as refractory and fatal complications. We investigated the consequences of chronic IL-33 stimulation and discovered a previously unrecognized mechanism that initiates pulmonary arterial remodeling. Repeated administration of IL-33 more than four weeks resulted in expansion of ILC2s and eosinophil accumulation around arteries and occlusive arterial hypertrophy in lung, but not in spleen, liver or kidney. The occlusive arteriopathy was ameliorated in Il5- or eosinophil-deficient mice, but not in Rag2-deficient mice, indicating IL-5 from ILC2s and eosinophils play pivotal roles in the pathogenesis. Administration of iloprost, an analogue of prostacyclin and vasodilator used in therapy for PAH, repressed the expansion of IL-5-producing ILC2s and pulmonary arteriopathy. We have identified several genes strongly induced in lung by chronic IL-33 administration, and will discuss the roles in lung remodeling and functions.


Reference:
Mo-ES2-2
Session:
Sponsored Evening Symposium 1, Sponsored by Kyowa Hakko Kirin Co., Ltd.
Presenter/s:
Satoshi Takaki
Presentation type:
Invited Speaker
Room:
ANA Crowne Plaza “Ohtori” Room B
Chair/s:
Kristin M. Leiferman, Kiyoshi Takatsu
Date:
Monday, 30 October 2017
Time:
17:30 - 18:00
Session times:
17:00 - 19:00