TY - JOUR
T1 - An Interleukin-33-Mast Cell-Interleukin-2 Axis Suppresses Papain-Induced Allergic Inflammation By Promoting Regulatory T Cell Numbers
AU - Morita, Hideaki
AU - Arae, Ken
AU - Unno, Hirotoshi
AU - Miyauchi, Kousuke
AU - Toyama, Sumika
AU - Nambu, Aya
AU - Oboki, Keisuke
AU - Ohno, Tatsukuni
AU - Motomura, Kenichiro
AU - Matsuda, Akira
AU - Yamaguchi, Sachiko
AU - Narushima, Seiko
AU - Kajiwara, Naoki
AU - Iikura, Motoyasu
AU - Suto, Hajime
AU - McKenzie, Andrew N.J.
AU - Takahashi, Takao
AU - Karasuyama, Hajime
AU - Okumura, Ko
AU - Azuma, Miyuki
AU - Moro, Kazuyo
AU - Akdis, Cezmi A.
AU - Galli, Stephen J.
AU - Koyasu, Shigeo
AU - Kubo, Masato
AU - Sudo, Katsuko
AU - Saito, Hirohisa
AU - Matsumoto, Kenji
AU - Nakae, Susumu
PY - 2015/7/21
Y1 - 2015/7/21
N2 - 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) tosecrete Th2 type-cytokines, MCs are thought tocooperate with NH cells in enhancing protease orIL-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.
AB - 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) tosecrete Th2 type-cytokines, MCs are thought tocooperate with NH cells in enhancing protease orIL-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.
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U2 - 10.1016/j.immuni.2015.06.021
DO - 10.1016/j.immuni.2015.06.021
M3 - Article
C2 - 26200013
AN - SCOPUS:84937697152
VL - 43
SP - 175
EP - 186
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 1
ER -