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

Author

Listed:
  • Tatsuya Saitoh

    (Laboratory of Host Defense,
    Department 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,
    Department of Host Defense,)

  • Bo-Gie Yang

    (Laboratory of Host Defense,
    Department of Host Defense,)

  • Takashi Satoh

    (Laboratory of Host Defense,
    Department 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
    Juntendo University School of Medicine, 2-1-1 Hongo Bunkyo-ku, Tokyo 113-8421, Japan
    PRESTO, Japan Science and Technology Corporation, Kawaguchi, Saitama 332-0012, 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,
    Department of Host Defense,)

  • Tohru Tsujimura

    (Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan)

  • Osamu Takeuchi

    (Laboratory of Host Defense,
    Department of Host Defense,)

  • Tamotsu Yoshimori

    (Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan
    CREST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan)

  • Shizuo Akira

    (Laboratory of Host Defense,
    Department of Host Defense,)

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.

Suggested Citation

  • 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 Ts, 2008. "Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1β production," Nature, Nature, vol. 456(7219), pages 264-268, November.
  • Handle: RePEc:nat:nature:v:456:y:2008:i:7219:d:10.1038_nature07383
    DOI: 10.1038/nature07383
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    Cited by:

    1. Kelvin Ka Lok Wu & KeKao Long & Huige Lin & Parco Ming Fai Siu & Ruby Lai Chong Hoo & Dewei Ye & Aimin Xu & Kenneth King Yip Cheng, 2021. "The APPL1-Rab5 axis restricts NLRP3 inflammasome activation through early endosomal-dependent mitophagy in macrophages," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    2. Man Chen & Madhav C. Menon & Wenlin Wang & Jia Fu & Zhengzi Yi & Zeguo Sun & Jessica Liu & Zhengzhe Li & Lingyun Mou & Khadija Banu & Sui-Wan Lee & Ying Dai & Nanditha Anandakrishnan & Evren U. Azelog, 2023. "HCK induces macrophage activation to promote renal inflammation and fibrosis via suppression of autophagy," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    3. Lauriane Galle-Treger & Doumet Georges Helou & Christine Quach & Emily Howard & Benjamin P. Hurrell & German R. Aleman Muench & Pedram Shafiei-Jahani & Jacob D. Painter & Andrea Iorga & Lily Dara & Ju, 2022. "Autophagy impairment in liver CD11c+ cells promotes non-alcoholic fatty liver disease through production of IL-23," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    4. Lucia Taraborrelli & Yasin Şenbabaoğlu & Lifen Wang & Junghyun Lim & Kerrigan Blake & Noelyn Kljavin & Sarah Gierke & Alexis Scherl & James Ziai & Erin McNamara & Mark Owyong & Shilpa Rao & Aslihan Ka, 2023. "Tumor-intrinsic expression of the autophagy gene Atg16l1 suppresses anti-tumor immunity in colorectal cancer," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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