Details

Autor(en) / Beteiligte

• Shindo, Ryodai
• Ohmuraya, Masaki
• Komazawa-Sakon, Sachiko
• Miyake, Sanae
• Deguchi, Yutaka
• Yamazaki, Soh
• Nishina, Takashi
• Yoshimoto, Takayuki
• Kakuta, Soichiro
• Koike, Masato
• Uchiyama, Yasuo
• Konishi, Hiroyuki
• Kiyama, Hiroshi
• Mikami, Tetuo
• Moriwaki, Kenta
• Araki, Kimi
• Nakano, Hiroyasu

Titel

Necroptosis of Intestinal Epithelial Cells Induces Type 3 Innate Lymphoid Cell-Dependent Lethal Ileitis

Ist Teil von

• iScience, 2019-05, Vol.15, p.536-551

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• A short form of cellular FLICE-inhibitory protein encoded by CFLARs promotes necroptosis. Although necroptosis is involved in various pathological conditions, the detailed mechanisms are not fully understood. Here we generated transgenic mice wherein CFLARs was integrated onto the X chromosome. All male CFLARs Tg mice died perinatally due to severe ileitis. Although necroptosis was observed in various tissues of CFLARs Tg mice, large numbers of intestinal epithelial cells (IECs) died by apoptosis. Deletion of Ripk3 or Mlkl, essential genes of necroptosis, prevented both necroptosis and apoptosis, and rescued lethality of CFLARs Tg mice. Type 3 innate lymphoid cells (ILC3s) were activated and recruited to the small intestine along with upregulation of interleukin-22 (Il22) in CFLARs Tg mice. Deletion of ILC3s or Il22 rescued lethality of CFLARs Tg mice by preventing apoptosis, but not necroptosis of IECs. Together, necroptosis-dependent activation of ILC3s induces lethal ileitis in an IL-22-dependent manner. [Display omitted] •CFLARs Tg mice develop severe ileitis in utero•Intestinal epithelial cells die by apoptosis and necroptosis in CFLARs Tg mice•Blockade of necroptosis rescues lethality of CFLARs Tg mice•Necroptosis activates type 3 innate lymphoid cells, resulting in severe ileitis Immunology; Immune Response; Cell Biology; Functional Aspects of Cell Biology