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

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

doi:10.1016/j.immuni.2015.06.021

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

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

Department of Pediatrics

Research output: Contribution to journal › Article

121 Citations (Scopus)

Abstract

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 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.

Original language	English
Pages (from-to)	175-186
Number of pages	12
Journal	Immunity
Volume	43
Issue number	1
DOIs	https://doi.org/10.1016/j.immuni.2015.06.021
Publication status	Published - 2015 Jul 21

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ASJC Scopus subject areas

Immunology and Allergy
Infectious Diseases
Immunology

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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, A. N. J., Takahashi, T., Karasuyama, H., Okumura, K., ... Nakae, S. (2015). An Interleukin-33-Mast Cell-Interleukin-2 Axis Suppresses Papain-Induced Allergic Inflammation By Promoting Regulatory T Cell Numbers. Immunity, 43(1), 175-186. https://doi.org/10.1016/j.immuni.2015.06.021

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

In: Immunity, Vol. 43, No. 1, 21.07.2015, p. 175-186.

Research output: Contribution to journal › Article

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, ANJ, 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 2015, 'An Interleukin-33-Mast Cell-Interleukin-2 Axis Suppresses Papain-Induced Allergic Inflammation By Promoting Regulatory T Cell Numbers', Immunity, vol. 43, no. 1, pp. 175-186. https://doi.org/10.1016/j.immuni.2015.06.021

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. / An Interleukin-33-Mast Cell-Interleukin-2 Axis Suppresses Papain-Induced Allergic Inflammation By Promoting Regulatory T Cell Numbers. In: Immunity. 2015 ; Vol. 43, No. 1. pp. 175-186.

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abstract = "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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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.

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10.1016/j.immuni.2015.06.021