Basophil-derived interleukin-4 controls the function of natural helper cells, a member of ILC2s, in lung inflammation.
Allergic asthma is an inflammatory disease characterized by lung eosinophilia controlled by type 2 cytokines. Cysteine proteases are potent triggers of allergic inflammation by causing barrier disruption in lung epithelial cells inducing the elevation of interleukin-5 (IL-5) and IL-13 from natural helper (NH) cells, a member of ILC2s, which leads to lung eosinophilia. In this study, we found that basophils play a crucial role in NH cell-mediated eosinophilic inflammation induced by protease allergens. Conditional deletion of basophils caused a resolution of the papain-induced eosinophilia and mucus production. Resolution of eosinophilia was also observed in mice lacking IL-4 specifically in basophils, indicating that basophil-derived IL-4 enhanced expression of the chemokine CCL11, as well as IL-5, IL-9, and IL-13 in NH cells, thus attracting eosinophils. These results demonstrate that IL-4 from basophils has an important role in the NH-derived cytokine and chemokine expression, subsequently leading to protease allergen-induced airway inflammation.
Division of Molecular Pathology, Research Institute for Biomedical Science, Tokyo University of Science, 2669 Yamazaki, Noda-shi, Chiba, 278-0022, Japan; Laboratory for Cytokine Regulation, RIKEN Center for Integrative Medical Sciences (IMS), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
Yasutaka
Y
Motomura
Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan.
Hideaki
H
Morita
Laboratory for Immune Cell System, RIKEN Center for Integrative Medical Sciences (IMS), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan; Division of Immunobiology, Department of Medical Life Science, Graduate School of Medical Life Science, Yokohama City University, 1-7-29 Suehiro-cho, Yokohama 230-0045, Japan; Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, 7 Goban-cho, Chiyoda-ku, Tokyo 102-0076, Japan.
Kazuyo
K
Moro
Laboratory of Systems Biology, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
Susumu
S
Nakae
Department of Microbiology, Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, 356 BRB, Philadelphia, PA 19104, USA.
David
D
Artis
Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences (IMS), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
Takaho A
TA
Endo
Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences (IMS), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
Yoko
Y
Kuroki
Laboratory for Integrative Genomics, RIKEN Center for Integrative Medical Sciences (IMS), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
Osamu
O
Ohara
Laboratory for Immune Cell System, RIKEN Center for Integrative Medical Sciences (IMS), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
Shigeo
S
Koyasu
Division of Molecular Pathology, Research Institute for Biomedical Science, Tokyo University of Science, 2669 Yamazaki, Noda-shi, Chiba, 278-0022, Japan; Laboratory for Cytokine Regulation, RIKEN Center for Integrative Medical Sciences (IMS), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. Electronic address: raysolfc@rcai.riken.jp.
Masato
M
Kubo
D000818:Animals; D001249:Asthma / Q000276:immunology; D001491:Basophils / Q000276:immunology*; D054413:Chemokine CCL11 / Q000096:biosynthesis; D004804:Eosinophils / Q000276:immunology*; D018793:Interleukin-13 / Q000096:biosynthesis / Q000276:immunology*; D015847:Interleukin-4 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D015848:Interleukin-5 / Q000096:biosynthesis / Q000276:immunology*; D016906:Interleukin-9 / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011014:Pneumonia / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D018793:Interleukin-13; D015848:Interleukin-5; D016906:Interleukin-9; D015847:Interleukin-4