Expression of IL-33 in ocular surface epithelium induces atopic keratoconjunctivitis with activation of group 2 innate lymphoid cells in mice

• DOI: 10.1038/s41598-017-10227-y
• Publication Date: 2017-08-24T14:44:20Z
• Authors: Yasutomo Imai; Yuka Hosotani; Hiroto Ishikawa; Koubun Yasuda; Makoto Nagai; Orie Jitsukawa; Fumi Gomi; Kenji Nakanishi; Tomohiro Yoshimoto; Takahiro Nakamura; Kiyofumi Yamanishi
• Keywords: Chemokine CCL11; 0303 health sciences; Interleukin-13; Epithelium, Corneal; Keratin-14; Keratoconjunctivitis; Membrane Proteins; Interleukin-33; Article; Founder Effect; Immunity, Innate; Basophils; 3. Good health; Eosinophils; Disease Models, Animal; Mice; 03 medical and health sciences; Gene Expression Regulation; Animals; Interleukin-4; Lymphocytes; Mast Cells; Interleukin-5; Conjunctiva

AbstractIn a transgenic mouse line hK14mIL33tg, with the expression of interleukin-33 (IL-33) driven by a keratin 14 promoter, keratoconjunctivitis developed spontaneously between 18 and 22 weeks of age under specific-pathogen-free conditions. These mice showed blepharitis and corneal impairments, and the histology revealed epithelial thickening in the conjunctiva and the cornea with infiltration of eosinophils, mast cells and basophils. IL-5, IL-13 and CCL11 were abundant in lacrimal fluid in the mice, and the gene expressions of IL-4, IL-5, IL-13, IL-33, Prg2 and Mmcp8 were significantly increased in the cornea. Furthermore, group 2 innate lymphoid cells (ILC2) producing IL-5 and IL-13 were markedly increased in the cornea. These phenotypes closely resemble human atopic keratoconjunctivitis (AKC). The characteristic ocular phenotype in these mice strongly suggests that IL-33 is crucial for the development of AKC. The mouse line may be useful as a novel model for research and development of therapeutic strategies for AKC.