Activation of group 2 innate lymphoid cells exacerbates and confers corticosteroid resistance to mouse nasal type 2 inflammation

Morikawa, T., Fukuoka, A. , Matsushita, K., Koubun, Y., Iwasaki, N., Akasaki, S., Shigeharu, F. and Yoshimoto, T. (2017) Activation of group 2 innate lymphoid cells exacerbates and confers corticosteroid resistance to mouse nasal type 2 inflammation. International Immunology, 29(5), pp. 221-233. (doi: 10.1093/intimm/dxx030) (PMID:28541554)

Abstract

Both Th2 cells and group 2 innate lymphoid cells (ILC2s) contribute to allergic diseases. However, their exact role and relationship in nasal allergic disorders are unclear. In this study, we investigated the cooperation of Th2 cells and ILC2s in a mouse model of nasal allergic disorder. To differentially activate Th2 cells and/or ILC2s in nasal mucosa, mice were intra-nasally administered ovalbumin (OVA) antigen, papain, an ILC2-activator, or both for 2 weeks. Epithelial thickness and number of eosinophils in the nasal mucosa were evaluated at 24 h after the final challenge. Intra-nasal administration of OVA and papain preferentially activated Th2 cells and ILC2s, respectively, in the nose. Both OVA and papain increased the nasal epithelial thickness and number of eosinophils, and their coadministration significantly enhanced the symptoms. Although T-/B-cell-deficient mice showed severely decreased nasal symptoms induced by OVA or OVA-plus-papain, the mice still showed slight papain-induced nasal symptoms. In ILC2-deficient mice, OVA-plus-papain-induced nasal symptoms were suppressed to the same level as OVA-alone. Similarly, IL-33- and ST2-deficient mice showed decreased OVA-plus-papain-induced nasal symptoms. IL-5 induced eosinophilia only, but IL-13 contributed to both nasal epithelial thickening and eosinophilia induced by OVA-plus-papain. Dexamethasone ameliorated OVA-alone-induced nasal epithelial thickening. However, OVA-plus-papain-induced nasal epithelial thickening was only partially controlled by dexamethasone. These results demonstrate that IL-33/ST2-pathway-mediated ILC2 activation exacerbated Th2-cell-induced nasal inflammation by producing IL-13. Although Th2-cell-alone-induced nasal inflammation was controlled by corticosteroid treatment, the activation of ILC2s conferred treatment resistance. Therefore, ILC2s and their activators could be therapeutic targets for treatment-refractory nasal allergic disorders.

• Item Type: Articles
• Additional Information: This work was supported by the Ministry of Education, Culture, Sports, Science and Technology Grant-in-Aid for Scientific Research, the Strategic Research Foundation at Private Universities (Number S1001055) and the Japan Society for the Promotion of Science KAKENHI Grant-in-Aid for Scientific Research B (Number 24390253) to T.Y.; the Japan Society for the Promotion of Science KAKENHI Grant-in-Aid for Young Scientist B (Number 15K19139) to A.F.; the Naito Foundation to K.M.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Suzuki, Dr Ayumi
• Authors: Morikawa, T., Fukuoka, A., Matsushita, K., Koubun, Y., Iwasaki, N., Akasaki, S., Shigeharu, F., and Yoshimoto, T.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: International Immunology
• Publisher: Oxford University Press
• ISSN: 0953-8178
• ISSN (Online): 1460-2377