An Interleukin-33-Mast Cell-Interleukin-2 Axis Suppresses Papain-Induced Allergic Inflammation by Promoting Regulatory T Cell Numbers.
An Interleukin-33-Mast Cell-Interleukin-2 Axis Suppresses Papain-Induced Allergic Inflammation by Promoting Regulatory T Cell Numbers.
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DOI：
10.1016/j.immuni.2015.06.021
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发表时间：
2015-07-21
期刊：
影响因子：
32.4
通讯作者：
Nakae S
中科院分区：
文献类型：
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作者：
Morita H;Arae K;Unno H;Miyauchi K;Toyama S;Nambu A;Oboki K;Ohno T;Motomura K;Matsuda A;Yamaguchi S;Narushima S;Kajiwara N;Iikura M;Suto H;McKenzie AN;Takahashi T;Karasuyama H;Okumura K;Azuma M;Moro K;Akdis CA;Galli SJ;Koyasu S;Kubo M;Sudo K;Saito H;Matsumoto K;Nakae S
屋尘螨衍生的蛋白酶部分通过破坏上皮屏障功能而导致过敏性疾病。白细胞介素-33（IL-33）是由肺细胞在蛋白酶过敏原作用下产生的，通过激活天然辅助细胞（NH）分泌Th 2型细胞因子，诱导气道嗜酸性粒细胞增多。由于IL-33也可以诱导肥大细胞（MC）分泌Th 2型细胞因子，因此MC被认为与NH细胞协同增强蛋白酶或IL-33介导的先天性气道嗜酸性粒细胞增多症。然而，我们发现MC缺陷型KitW-sh/W-sh小鼠表现出与调节性T（Treg）细胞数量减少相关的蛋白酶诱导的肺部炎症加剧。此外，由IL-33刺激的MC产生的IL-2促进Treg细胞数量的扩增，从而抑制木瓜蛋白酶或IL-33诱导的气道嗜酸性粒细胞增多的发展。因此，我们已经确定了一个独特的抗炎途径，可以限制诱导先天型过敏性气道炎症介导的NH细胞。
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 KitW-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.