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
N1 - Funding Information:
We thank the members of NCH (M. Fujiwara, H. Wakita, Y. Shimamoto, S. Fukuda, M. Yamada, N. Hashimoto, K. Takeda, and N. Okada), IMSUT (W. Nakanishi, N. Hiraishi, E. Shimura, and A. Shibui), RIKEN (M. Mochizuki and N. Takeno), SIAF (B. Stanic and T. Kubo), and Dr. Jenny Mjösberg (Karolinska Institutet) for their technical assistance, and Drs. P. Besmer (Cornell University), S. Akira (Osaka University), K. Nakanishi (Hyogo College), S. Koyasu (RIKEN), and S. Ishido (RIKEN) for providing Kit W-sh/W-sh , myd88 −/− , Il1rl1 −/− , Il2 −/− , and H2-Ab1 −/− mice, respectively. We are grateful to Lawrence W. Stiver (Tokyo, Japan) for critical reading of the manuscript. This work was supported by Grants-in-Aid for Young Scientists (B) (H.M., T.O., and K.O.), a Grant-in-Aid for Scientific Research (B) (H. Saito and K. Matsumoto) and (S) (S.K.), a Grant-in-Aid for Challenging Exploratory Research (S.K.), PRESTO, the Japan Science and Technology Agency (K. Moro and S. Nakae) from the Japan Society for the Promotion of Science , a Grant-in-Aid for Scientific Research on Innovative Areas (K. Moro) and the Program for Improvement of Research Environment for Young Researchers, The Special Coordination Funds for Promoting Science and Technology (S. Nakae) from the Ministry of Education, Culture, Sports, Science and Technology, Japan , Health Labour Sciences Research Grant from the Ministry of Health, Labour and Welfare, Japan (H. Saito, S. Nakae, and K. Matsumoto), Banyu Life Science Foundation International (H.M.), Swiss National Science Foundation No. 320030-140772 (C.A.A.), and NIH grants AI070813 , AI023990 , CA072074 , and U19AI104209 (S.J.G.).
Publisher Copyright:
© 2015 Elsevier Inc.
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
SN - 1074-7613
VL - 43
SP - 175
EP - 186
JO - Immunity
JF - Immunity
IS - 1
ER -
