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Regenerating islet-derived protein (Reg)3β plays a crucial role in attenuation of ileitis and colitis in mice

2020; Elsevier BV; Volume: 21; Linguagem: Inglês

10.1016/j.bbrep.2020.100738

2405-5808

Ryodai Shindo, Takaharu Katagiri, Sachiko Komazawa‐Sakon, Masaki Ohmuraya, Wakami Takeda, Yoshiko Nakagawa, Naomi Nakagata, Tetsushi Sakuma, Takashi Yamamoto, Chiharu Nishiyama, Takashi Nishina, Soh Yamazaki, Hideto Kameda, Hiroyasu Nakano,

Immune Cell Function and Interaction

Regenerating islet-derived protein (Reg)3β belongs to a member of the Reg family of proteins and has pleiotropic functions, including antimicrobial activity and tissue repair. However, whether Reg3β plays a protective role in the development of colitis and ileitis has not been fully investigated. We generated transgenic mice expressing a short form of cellular FLICE-inhibitory protein (cFLIPs) that promotes necroptosis, a regulated form of cell death. cFLIPs transgenic (CFLARs Tg) mice develop severe ileitis in utero. Although Reg3β is undetectable in the small intestine of wild-type embryos, its expression is aberrantly elevated in the small intestine of CFLARs Tg embryos. To test whether elevated Reg3β attenuates or exacerbates ileitis in CFLARs Tg mice, we generated a Reg3b-/- strain. Reg3b-/- mice grew to adulthood without apparent abnormalities. Deletion of Reg3b in CFLARs Tg mice exacerbated the embryonic lethality of CFLARs Tg mice. Dextran sulfate sodium-induced colitis, characterized by body weight loss and infiltration of neutrophils, was exacerbated in Reg3b-/- compared to wild-type mice. Moreover, the expression of Interleukin 6, an inflammatory cytokine and Chitinase-like 3, a marker for tissue repair macrophages was elevated in the colon of Reg3b-/- mice compared to wild-type mice after DSS treatment. Together, these results suggest that attenuation of colitis and ileitis is a result of Reg3β's real function.