An Interleukin-33-Mast Cell-Interleukin-2 Axis Suppresses Papain-Induced Allergic Inflammation by Promoting Regulatory T Cell Numbers

作者：Morita Hideaki; Arae Ken; Unno Hirotoshi; Miyauchi Kousuke; Toyama Sumika; Nambu Aya; Oboki Keisuke; Ohno Tatsukuni; Motomura Kenichiro; Matsuda Akira; Yamaguchi Sachiko; Narushima Seiko; Kajiwara Naoki; Iikura Motoyasu; Suto Hajime; McKenzie Andrew N J; Takahashi Takao; Karasuyama Hajime; Okumura Ko; Azuma Miyuki; Moro Kazuyo; Akdis Cezmi A; Galli Stephen J; Koyasu Shigeo; Kubo Masato; Sudo Katsuko; Saito Hirohisa; Matsumoto Kenji; Nakae Susumu^*

来源：Immunity, 2015, 43(1): 175-186.

DOI：10.1016/j.immuni.2015.06.021

House dust mite-derived proteases contribute to allergic disorders in part by disrupting epithelial barrier function. Interleukin-33 (IL-33), produced by lung cells after exposure to protease allergens, can induce innate-type airway eosinophilia by activating natural helper (NH) cells, a member of group 2 innate lymphoid cells (ILC2), to secrete Th2 type-cytokines. Because IL-33 also can induce mast cells (MCs) to secrete Th2 type-cytokines, MCs are thought to cooperate with NH cells in enhancing protease or IL-33-mediated innate-type airway eosinophilia. However, we found that MC-deficient Kit(W-sh/W-sh) mice exhibited exacerbated protease-induced lung inflammation associated with reduced numbers of regulatory T (Treg) cells. Moreover, IL-2 produced by IL-33-stimulated MCs promoted expansion of numbers of Treg cells, thereby suppressing development of papain-or IL-33-induced airway eosinophilia. We have thus identified a unique anti-inflammatory pathway that can limit induction of innate-type allergic airway inflammation mediated by NH cells.

• 出版日期2015-7-21
• 单位河北医科大学