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

Research output: Contribution to journalArticle

139 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 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.

Original languageEnglish
Pages (from-to)175-186
Number of pages12
JournalImmunity
Volume43
Issue number1
DOIs
Publication statusPublished - 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