Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1β production

Tatsuya Saitoh, Naonobu Fujita, Myoung Ho Jang, Satoshi Uematsu, Bo-Gie Yang, Takashi Satoh, Hiroko Omori, Takeshi Noda, Naoki Yamamoto, Masaaki Komatsu, Keiji Tanaka, Taro Kawai, Tohru Tsujimura, Osamu Takeuchi, Tamotsu Yoshimori and Shizuo Akira ()
Additional contact information
Tatsuya Saitoh: Laboratory of Host Defense,
Naonobu Fujita: Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan
Myoung Ho Jang: Laboratory of Gastrointestinal Immunology, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan
Satoshi Uematsu: Laboratory of Host Defense,
Bo-Gie Yang: Laboratory of Host Defense,
Takashi Satoh: Laboratory of Host Defense,
Hiroko Omori: Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan
Takeshi Noda: Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan
Naoki Yamamoto: AIDS Research Center, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan
Masaaki Komatsu: Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 113-8613, Japan
Keiji Tanaka: Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 113-8613, Japan
Taro Kawai: Laboratory of Host Defense,
Tohru Tsujimura: Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan
Osamu Takeuchi: Laboratory of Host Defense,
Tamotsu Yoshimori: Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan
Shizuo Akira: Laboratory of Host Defense,

Nature, 2008, vol. 456, issue 7219, 264-268

Abstract: Inflammatory bowel disease Crohn's disease, a chronic inflammation of the gut, has been linked to over thirty gene loci. Two papers in this issue focus a recent addition to that list, ATG16L1 (Atg16-like 1). Atg16 protein itself was first identified in yeast as an essential gene for the process of autophagy, a system that clears away unwanted cellular components and is involved in the pathogenesis of microbial infection, neurodegeneration and tumorigenesis. Cadwell et al. report a unique role for Atg16L1 in Paneth cells, a type of epithelial cell that secretes granules containing antimicrobial peptides into the intestines. Saitoh et al. show that ATG16L1 plays a role in the inflammatory response in isolated macrophages and in the mouse intestine, as an essential component of the autophagic machinery. This work implicates Atg16L1 in the control of inflammatory immune response and the maintenance of intestinal barrier, both of which are important for the prevention of inflammatory bowel disease.

Date: 2008
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DOI: 10.1038/nature07383

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