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 › peer-review

148 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

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Infectious Diseases

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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 › peer-review

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

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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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

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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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