Interleukin 11 confers resistance to dextran sulfate sodium-induced colitis in mice

Takashi Nishina; Yutaka Deguchi; Mika Kawauchi; Chen Xiyu; Soh Yamazaki; Tetuo Mikami; Hiroyasu Nakano

doi:10.1016/j.isci.2023.105934

Interleukin 11 confers resistance to dextran sulfate sodium-induced colitis in mice

iScience. 2023 Jan 5;26(2):105934. doi: 10.1016/j.isci.2023.105934. eCollection 2023 Feb 17.

Authors

Takashi Nishina¹, Yutaka Deguchi¹, Mika Kawauchi¹, Chen Xiyu^{1

2}, Soh Yamazaki¹, Tetuo Mikami³, Hiroyasu Nakano^{1

4}

Affiliations

¹ Department of Biochemistry, Toho University School of Medicine, 5-21-16 Omori-Nishi, Ota-ku, Tokyo 143-8540, Japan.
² Tokyo College of Biotechnology, 1-3-14 Kitakoujiya, Ota-ku, Tokyo 144-0032, Japan.
³ Department of Pathology, Toho University School of Medicine, 5-21-16 Omori-Nishi, Ota-ku, Tokyo 143-8540, Japan.
⁴ Host Defense Research Center, Toho University School of Medicine, 5-21-16 Omori-Nishi, Ota-ku, Tokyo 143-8540, Japan.

Abstract

Intestinal homeostasis is tightly regulated by epithelial cells, leukocytes, and stromal cells, and its dysregulation is associated with inflammatory bowel diseases. Interleukin (IL)-11, a member of the IL-6 family of cytokines, is produced by inflammatory fibroblasts during acute colitis. However, the role of IL-11 in the development of colitis is still unclear. Herein, we showed that IL-11 ameliorated DSS-induced acute colitis in mouse models. We found that deletion of Il11ra1 or Il11 rendered mice highly susceptible to DSS-induced colitis compared to the respective control mice. The number of apoptotic epithelial cells was increased in DSS-treated Il11ra1- or Il11-deficient mice. Moreover, we showed that IL-11 production was regulated by reactive oxygen species (ROS) produced by lysozyme M-positive myeloid cells. These findings indicate that fibroblast-produced IL-11 plays an important role in protecting the mucosal epithelium in acute colitis. Myeloid cell-derived ROS contribute to the attenuation of colitis through the production of IL-11.

Keywords: Components of the immune system; Immunology; Molecular physiology.