Function of Inducible Transcriptional Regulators in Regulation of Inflammatory Reactions in Homeostasis and Its Dysregulation.

2011 Fiscal Year Final Research Report

• Project/Area Number: 21390088
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Tohoku University
• Principal Investigator: MUTA Tatsushi 東北大学, 大学院・生命科学研究科, 教授 (60222337)
• Co-Investigator(Renkei-kenkyūsha): OHBA Tomoyuki 東北大学, 大学院・生命科学研究科, 助教 (80380666)
• Project Period (FY): 2009 – 2011
• Keywords: 分子病態学

Research Abstract

IκB-ζ gene-deficient mice spontaneously develop chronic inflammation around eyes. In this study, we analyzed the chronic inflammation of the mutant mice. We revealed that the inflammation was caused by an autoimmune disease resembling human Sjogren's syndrome, that although lymphocytes were required for the development of the inflammation, IκB-ζ-deficiency in epithelial cells, but not abnormality of the lymphocytes was the main causes of the disease, and that enhanced apoptosis was induced in IκB-ζ-deficient lacrimal glands, which resulted in activation of autoreactive lymphocytes. These results will greatly contribute to the understanding of pathogenic mechanism and development of therapy for Sjogren's syndrome.

Research Products

• [Journal Article] Transcriptional and Post-transcriptional Regulationof IκB-ζ upon Engagement of BCR (2013)
  • Author(s): Hanihara, F., Takahashi, Y., Okuma, A., Ohba, T., and Muta, T
  • Journal Title: TLRand FcγreceptorInt Immunol
  • DOI: doi:10.1093/intimm/dxt017
  • Peer Reviewed
• [Journal Article] Thioredoxin-Interacting Protein Gene Expression via MondoA Is Rapidly and Transiently Suppressed during Inflammatory Responses (2013)
  • Author(s): Kanari Y, Sato Y, Aoyama S, Muta T
  • Journal Title: PLoS One Volume: 8(3) Pages: e59026
  • DOI: doi:10.1371/journal.pone.0059026. Epub2013 Mar 8.
  • Peer Reviewed
• [Journal Article] Enhanced Apoptosis by Disruption of the STAT3-IκB-ζ Signaling Pathway in Epithelial Cells Induces Sjogren's Syndrome-like Autoimmune Disease (2013)
  • Author(s): Okuma A, Hoshino K, Ohba T, Fukushi S, Aiba S, Akira S, Ono M, Kaisho T, Muta T.
  • Journal Title: Immunity Volume: 38(3) Pages: 450-60
  • DOI: DOI:10.1016/j.immuni.2012.11.016. Epub 2013 Feb 28.
  • Peer Reviewed
• [Journal Article] Interleukin-10-induced neutrophil gelatinase-associated lipocalin production in macrophages with consequences for tumor growth (2012)
  • Author(s): Jung M, Weigert A, Tausendschon M, Mora J, Oren B, Sola A, Hotter G, Muta T, Brune B
  • Journal Title: Mol Cell Biol Volume: 32(19) Pages: 3938-48
  • DOI: doi:10.1128/MCB.00413-12. Epub 2012 Jul30.
  • Peer Reviewed
• [Journal Article] Identification of interleukin-1 receptor-associated kinase 1 as a critical component that induces post-transcriptional activation of IκB-ζ (2012)
  • Author(s): Ohba T, Ariga Y, Maruyama T, Truong NK, Inoue J, Muta T
  • Journal Title: FEBS J Volume: 279(2) Pages: 211-22
  • DOI: doi:10.1111/j.1742-4658.2011.08416.x. Epub 2011 Nov 30.
  • Peer Reviewed
• [Journal Article] IκBζ is essential for natural killer cell activation in response to IL-12and IL-18 (2010)
  • Author(s): Miyake T, Satoh T, Kato H, Matsushita K, Kumagai Y, Vandenbon A, Tani T, Muta T, Akira S, Takeuchi O.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 107(41) Pages: 17680-5
  • Peer Reviewed
• [Journal Article] IκBζ regulates T_H17 development bycooperating with ROR nuclear receptors (2010)
  • Author(s): Okamoto K, Iwai Y, Oh-Hora M, Yamamoto M, Morio T, Aoki K, Ohya K, Jetten AM, Akira S, Muta T, Takayanagi H
  • Journal Title: Nature Volume: 464(7293) Pages: 1381-5
  • DOI: doi:10.1038/nature08922
  • Peer Reviewed
• [Presentation] Roles for the nuclear IκB family protein IκB-ζ in inflammation. (Invited) (2012)
  • Author(s): Tatsushi Muta
  • Organizer: 第85回日本生化学会大会(招待講演)
  • Place of Presentation: 福岡
  • Year and Date: 20121214-16
• [Presentation] Regulation of inflammatory gene expression by the nuclear IκB family protein IκB-ζ. (Invited)The 12th Biennial International Endotoxin and Innate Immunity Society MeetingThe Homeostatic Inflammation Symposium (2012)
  • Author(s): Tatsushi Muta
  • Organizer: The 18th Japan Endotoxin and InnateImmunity Society Meeting The 11th Japanese Biochemical SocietyBio-Frontier Meeting
  • Place of Presentation: Tokyo
  • Year and Date: 20121023-26
• [Presentation] Transcriptional and Post-transcriptional Activation of IκB-ζ by Toll-like Receptor and B Cell Antigen Receptor. (Poster) (2012)
  • Author(s): Fumito Hanihara and Tatsushi Muta
  • Organizer: The 12th Biennial International Endotoxin and Innate Immunity Society Meeting
  • Place of Presentation: Tokyo
  • Year and Date: 20121023-26
• [Presentation] IκB-ζ-deficient Mice Develop Sjogren's Syndrome-like Chronic Inflammation Caused by Dysregulation of Epithelial Homeostasis. (Poster) (2012)
  • Author(s): Atsushi Okuma, Katsuaki Hoshino, Tsuneyasu Kaisho and Tatsushi Muta
  • Organizer: The 12th Biennial International Endotoxin and Innate Immunity Society Meeting
  • Place of Presentation: Tokyo
  • Year and Date: 20121023-26
• [Presentation] 感染防御応答における多段階遺伝子発 (2012)
  • Author(s): 牟田達史
  • Organizer: 現制御機構第85回日本細菌学会総会(招待講演)
  • Place of Presentation: 長崎
  • Year and Date: 20120327-29
• [Presentation] Chemokine Induction in Macrophages as a Response to Necrotic Cells (2011)
  • Author(s): Kimura, T., Watanabe, E., Hanihara, F., Ohba, T., and ○Muta, T.
  • Organizer: Toll2011 Meeting-Decoding InnateImmunity (Poster)
  • Place of Presentation: Riva del Garda, Italy
  • Year and Date: 20110504-07
• [Presentation] 炎症応答における核内IκB-ζファミリータ ンパク質IκB-ζの機能とその破綻 (2011)
  • Author(s): 牟田達史
  • Organizer: The 7th Tsukuba Hematologic DiseaseSeminar in Autumn, 2011(招待講演)
  • Place of Presentation: つくば
  • Year and Date: 2011-09-15
• [Presentation] Stimulus-specificPost-transcriptional Regulation of IκB-ζ in Innate and Adaptive Immune Responses (2010)
  • Author(s): Hanihara, F., Takahashi, Y., Ohba, T., and Muta, T.
  • Organizer: 2010 Joint Annual Meeting between the Society for Leukocyte Biology and the International Endotoxin & Innate Immunity Society
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 20101006-09
• [Presentation] Roles for Lymphocytes and Non-hematopoietic Cells in the Pathogenesis of Chronic Skin Inflammation in IκB-ζdeficient Mice (2010)
  • Author(s): Okuma, A., Ohba, T., and Muta, T.
  • Organizer: 2010 Joint Annual Meeting between the Society for Leukocyte Biology and the International Endotoxin & Innate Immunity Society
  • Place of Presentation: Vancouver, BC, Canada
  • Year and Date: 20101006-09
• [Presentation] Chemokines Induction of Macrophages in Response to Dead Cells (2010)
  • Author(s): Kimura, T., Watanabe, E., Hanihara, F., Ohba, T. and Muta, T
  • Organizer: 14th International Congress of Immunology (Poster)
  • Place of Presentation: Kobe, Japan
  • Year and Date: 20100822-27
• [Presentation] Analysis on the Pathogenesis of Chronic Skin Inflammation that Spontaneously Develops in IκB-ζ Gene-deficient Mice (2010)
  • Author(s): Okuma, A., Ohba, T., Ono, M., Shibuya, S., Aiba, S., and Muta, T
  • Organizer: 14th International Congress of Immunology (Poster)
  • Place of Presentation: Kobe, Japan
  • Year and Date: 20100822-27
• [Presentation] Stimulus-specific Post-transcriptional Regulation of IκB-ζ, an Essential Regulator on Inflammatory Responses (2010)
  • Author(s): Hanihara, F., Takahashi, Y., Ohba, T., and Muta, T.
  • Organizer: 14th International Congress of Immunology (Poster)
  • Place of Presentation: Kobe, Japan
  • Year and Date: 20100822-27
• [Presentation] Molecular Dissection of the MyD88-dependent Signaling that Leads to Specific mRNA Stabilization (2010)
  • Author(s): Ariga, Y., Hanihara, F., Ohba, T., and Muta, T.
  • Organizer: Keystone Symposium "Innate Immunity"
  • Place of Presentation: Dublin, Ireland
  • Year and Date: 20100707-12
• [Presentation] 自然免疫における炎症応答制御とその破綻 (2010)
  • Author(s): 牟田達史
  • Organizer: 第33回日本血栓止血学会学術集会(ランチョンセミナー、招待講演)
  • Place of Presentation: 鹿児島
  • Year and Date: 20100422-24
• [Presentation] Chronic Skin Inflammation Developed in Mice Lacking IκB-ζ, a Crucial NF-κB Regulator (2010)
  • Author(s): Okuma, A., Ohba, T., and Muta, T.
  • Organizer: Keystone Symposium "NF-κB in Inflammation and Disease" (Poster)
  • Place of Presentation: Santa Fe, NewMexico, USA
  • Year and Date: 20100105-10
• [Presentation] 誘導型転写制御因子IκB-ζによる炎症応答制御とその破綻により自然発症する慢性炎症 (2009)
  • Author(s): 牟田達史
  • Organizer: 第82回日本生化学会大会シンポジウム4S2p「自然炎症」-病原体センサーと内因性リガンドによる非感染性炎症反応の分子基盤-(招待講演)
  • Place of Presentation: 神戸
  • Year and Date: 20091021‐24
• [Presentation] 自然免疫による感染微生物に対する認識・応答とその制御の分子機構 (2009)
  • Author(s): 牟田達史
  • Organizer: 第32回日本血栓止血学会学術集会(招待講演)
  • Place of Presentation: 北九州
  • Year and Date: 20090604-06
• [Presentation] 誘導型転写制御因子IκB-ζによる炎症応答における選択的遺伝子発現機構 (2009)
  • Author(s): 牟田達史
  • Organizer: 第8回四国免疫フォーラム(特別講演)
  • Place of Presentation: 高松
  • Year and Date: 2009-06-27
• [Book] 核内IκBタンパク質IκB-ζを介したサイトカイン産生制御 (2010)
  • Author(s): 牟田達史
  • Total Pages: 1863-1868
  • Publisher: 実験医学(増刊)
• [Book] 核内IκB蛋白質IκB-ζを介したサイトカイン産生制御 (2010)
  • Author(s): 牟田達史
  • Total Pages: 372-378
  • Publisher: 医学のあゆみ
• [Book] 炎症における転写制御とその破綻 (2010)
  • Author(s): 牟田達史
  • Total Pages: 228-233
  • Publisher: 炎症と免疫
• [Remarks] (1) 東北大学大学院生命科学研究科牟田研究室
  • URL: http://www.biology.tohoku.ac.jp/lab- www/muta_lab/
• [Remarks] (2)東北大学プレスリリース組織特異的自己免疫疾患の病因解明(上皮細胞の過剰な細胞死によってシェーグレン症候群が誘導される)
  • URL: http://www.tohoku.ac.jp/japanese/2013/03/press20130228-02.html
• [Remarks] (3)東北大学大学院生命科学研究科研究成果
  • URL: http://www.lifesci.tohoku.ac.jp/research_ja/14954/