Role of Atg5-dependent autophagy in innate immunity of epidermal keratinocytes

• Project/Area Number: 22390218
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dermatology
• Research Institution: Ehime University
• Principal Investigator: SAYAMA Koji 愛媛大学, 大学院・医学系研究科, 教授 (80187286)
• Co-Investigator(Renkei-kenkyūsha): SHIRAKATA Yuji 愛媛大学, 大学院・医学系研究科, 准教授 (50226320) ; HANAKAWA Yasushi 愛媛大学, 大学院・医学系研究科, 講師 (90284398) ; OKUMARU Sho 愛媛大学, 大学院・医学系研究科, 講師 (50398046)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000); Fiscal Year 2012: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2011: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2010: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
• Keywords: 皮膚感染症 / 角化細 / 自然免疫 / オートファジー / Atg5 / 角化細胞 / ノックアウトマウス / 分化 / LC / K5-Cre

Research Abstract

Autophagy is a mechanism to degrade selective cellular components. Since autophagy is a mechanism degrading the intracellular components during starvation, autophagy may play an essential role in clearance of intracellular pathogens. The purpose of this study is to clarify the role of keratinocyte autophagy in innate immunity. Differentiation and starvation induced autophagy in cultured keratinocytes. Stimulation of Toll-like receptor ligands also induced autophagy, indicating that autophagy play an important role in epidermal innate immunity. The expression of LC3 was not altered in Atg5 KO mouse epidermis.

Research Products

• [Journal Article] INF-alpha Enhances IL-22 Receptor Expression in Keratinocytes:A Possible Role in the Development of Psoriasis. (2012)
  • Author(s): Tohyama M, Yang L, Hanakawa Y, Dai X, Shirakata Y, and Sayama K.
  • Journal Title: J Invest Dermatol; Volume: 132 Issue: 5 Pages: 1933-1935
  • DOI: 10.1007/s00109-009-0457-0
  • Peer Reviewed
• [Journal Article] Nuclear translocation of phosphorylated STAT3 regulates VEGF-A-induced lymphatic endothelial cell migration and tube formation (2011)
  • Author(s): Okazaki H, et al
  • Journal Title: Biochem Biophys Res Commun Volume: 412 Issue: 3 Pages: 441-5
  • DOI: 10.1016/j.bbrc.2011.07.111
  • Peer Reviewed
• [Journal Article] Mite allergen is a danger signal for the skin via activation of inflamasome in keratinocytes (2011)
  • Author(s): Dai X, Sayama K, Tohyama M, Shirakata Y, Hanakawa Y, Tokumaru S, Yang L, Hirakawa S, and Hashimoto K.
  • Journal Title: J Allergy Clin Immunol Volume: 127 Issue: 3 Pages: 806-814
  • DOI: 10.1016/j.jaci.2010.12.006
  • Peer Reviewed
• [Journal Article] Mite allergen is a danger signal for the skin via activation of the inflammasome in keratinocytes (2011)
  • Author(s): Dai, X
  • Journal Title: J Allergy Clin Immunol Volume: 127 Pages: 806-814
  • Peer Reviewed
• [Journal Article] Nuclear translocation of phosphorylated STAT3 regulates VEGF-A-induced lymphatic endothelial cell migration and tube formation (2011)
  • Author(s): Okazaki, H
  • Journal Title: Biochem Biophys Res Commun Volume: 412 Pages: 441-445
  • Peer Reviewed
• [Journal Article] Inflammatory mediator TAK1 regulates hair follicle morphogenesis and anagen induction shwn by using deratinocyte-specific TAK1-dificient mice (2010)
  • Author(s): Sayama K, Kajiya K, Sugawara K, Sato S, Hirakawa S, Shirakata Y, Hanakawa Y, Dai X, Ishimatsu-Tsuji Y, Metzger D, Chambon P, Akira S, Paus R, Kishimoto J, and Hashimoto K.
  • Journal Title: PloS One Volume: 5 Issue: 6 Pages: e11275-e11275
  • DOI: 10.1371/journal.pone.0011275
  • Peer Reviewed
• [Journal Article] PPARγmediates innate immunity by regulating the 1α, 25-dihydroxyvitamin D3 induced hBD-3 and cathelicidin in human keratinocytes (2010)
  • Author(s): Dai X, Sayama K, Tohyama M, Shirakata Y, Hanakawa Y, Tokumaru S, Yang L, Hirakawa S, and Hashimoto K.
  • Journal Title: J Dermatol Sci Volume: 60 Issue: 3 Pages: 179-186
  • DOI: 10.1016/j.jdermsci.2010.09.008
  • Peer Reviewed
• [Journal Article] E2 Polyubiquitin-conjugating enzyme Ubc13 in keratinocytes is essential for epidermal integrity (2010)
  • Author(s): Sayama K, Yamamoto M, Shirakata Y, Hanakawa Y, Hirakawa S, Dai X, Tohyama M, Tokumaru S, Shin MS, Sakurai H, Akira S, and Hashimoto K.
  • Journal Title: J Biol Chem; Volume: 285 Issue: 39 Pages: 30042-30049
  • DOI: 10.1074/jbc.m110.106484
  • Peer Reviewed
• [Journal Article] E2 polyubiquitin-conjugating enzyme Ubc13 in keratinocytes is essential for epidermal integrity. (2010)
  • Author(s): Sayama K
  • Journal Title: J Biol Chem Volume: 285 Pages: 30042-9
  • Peer Reviewed
• [Journal Article] PPAR-γ mediates innate immunity by regulating the 1α, 25-dihydroxyvitamin D3 induced hBD-3 and cathelicidin in human keratinocytes (2010)
  • Author(s): Dai X
  • Journal Title: J Dermatol Sci Volume: 60 Pages: 179-86
  • Peer Reviewed
• [Journal Article] Inflammatory mediator TAK1 regulates hair follicle morphogenesis and anagen induction shown by using keratinocyte-specific TAK1-deficient mice. (2010)
  • Author(s): Sayama K
  • Journal Title: PLoS One Volume: 5
  • Peer Reviewed
• [Presentation] Autophagy is induced by differentiation in epidermal keratinocytes. (2012)
  • Author(s): Dai X, Okazaki H, Hanakawa Y, Shirakata Y, Murakami M, Tohyama M, and Sayama K.
  • Organizer: 42ndAnnual ESDR Meeting
  • Place of Presentation: Venice, Italy
• [Presentation] Autophagy is an innate immune system of epidermal keratinocytes. (2012)
  • Author(s): Okazaki H, Dai X, Hanakawa Y, Shirakata Y, Tohyama M, and Sayama K
  • Organizer: SID Annual Meeting & 75thAnniversary Celebration
  • Place of Presentation: North Carolina. USA
• [Presentation] Intracellular dsRNA activates inflammasome in the keratinocytes resulting in the release of IL-18 (2012)
  • Author(s): Dai X, Shirakata T, Tohyama M, Hanakawa Y, Okazaki H, and Sayama K.
  • Organizer: SID Annual Meeting & 75thAnniversary Celebration
  • Place of Presentation: North Carolina. USA
• [Presentation] Autophagy is induced by differentiation in epidermal keratinocytes. (2012)
  • Author(s): Dai X, Okazaki H, Hanakawa Y, Shirakata Y, Murakami M, Tohyama M, and Sayama K.
  • Organizer: 42nd Annual ESDR Meeting
  • Place of Presentation: Venice, Italy
• [Presentation] Autophagy is an innate immune system of epidermal keratinocytes. (2012)
  • Author(s): Okazaki H, Dai X, Hanakawa Y, Shirakata Y, Tohyama M, and Sayama K.
  • Organizer: SID Annual Meeting
  • Place of Presentation: North Carolina, USA
• [Presentation] Intracellular dsRNA activates inflammasome in the keratinocytes resulting in the release of IL-18. (2012)
  • Author(s): Dai X, Shirakata T, Tohyama M, Hanakawa Y, Okazaki H, and Sayama K.
  • Organizer: SID Annual Meeting
  • Place of Presentation: North Carolina, USA
• [Presentation] Mite allergen activates inflammasome in epidermal keratinocytes resulting in the production of IL-1beta and IL-18 (2011)
  • Author(s): Dai, X
  • Organizer: 22^<nd> World Congress of Dermatology
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2011-05-28
• [Presentation] Mite allergen activates inflammasome in epidermal keratinocytes resulting in the production of IL-1beta and IL-18 (2011)
  • Author(s): Dai X, Sayama K, Tohyama M, Shirakata Y, Hanakawa Y, Tokumaru S, Yang L, Hirakawa S, and Hashimoto K
  • Organizer: 22ndWorld Congress of Dermatology
  • Place of Presentation: Seoul, Korea
• [Presentation] Nuclear translocation of Bcl3 and p50 by IL-22 produces HB-EGF, IL-8, S100A7, and human β-defensin 2 in keratinocytes of psoriasis. (2011)
  • Author(s): Tohyama M, Hanakawa Y, Shirakata Y, Dai X, Otani T, Hashimoto K, and Sayama K
  • Organizer: The 41st Annual ESDR Meeting
  • Place of Presentation: Barcelona, Spain
• [Presentation] Mite allergen is a danger signal for the skin (2010)
  • Author(s): Sayama K
  • Organizer: European Society for Investigative Dermatology
  • Place of Presentation: ヘルシンキ/フィンランド
  • Year and Date: 2010-09-10
• [Presentation] Mite allergen is a danger signal for the skin (2010)
  • Author(s): Sayama K, Dai X, Shirakata Y, Tohyama M, Miyawaki S, Hirakawa S, and Hashimoto K
  • Organizer: 40thAnnual ESDR Meeting of the European Society for Dermatological Research
  • Place of Presentation: Helsinki, Finland