Investigation of IL-23/Th17 axis in pathogenesis of psoriasis using a mouse model.

• Project/Area Number: 22591242
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dermatology
• Research Institution: Kochi University
• Principal Investigator: TAKAISHI Mikiro 高知大学, 教育研究部医療学系, 助教 (10303223)
• Co-Investigator(Kenkyū-buntansha): MIYOSHI Ken 高知大学, 教育研究部医療学系, 助教 (20274392) ; NAKAJIMA Kimiko 高知大学, 教育研究部医療学系, 講師 (20403892) ; SANO Shigetoshi 高知大学, 教育研究部医療学系, 教授 (80273621)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 乾癬 / モデルマウス / Th17 / IL-23 / IL-22 / Stat3 / IL-17

Research Abstract

The roles of IL-23 and IL-22 in pathogenesis of psoriasis were investigated using K5.Stat3C transgenic mice, as a unique mouse model for psoriasis. The development of psoriasis-like lesions was attenuated in the K5.Stat3C mice being deficient in IL-23 production. In other hands, the lesions in the IL-22 deficient mice were generated as same as in the control mice. The results indicated that IL-23 played a significant role in psoriasis and that some alternative pathways could compensate the loss of IL-22 in development of psoriasis-like lesions.

Research Products

• [Journal Article] Barrier abnormality due to ceramide deficiency leads to psoriasiform inflammation in a mouse model. (2013)
  • Author(s): Nakajima K, Terao M, Takaishi M, Kataoka S, Goto-Inoue N, Setou M, Horie K, Sakamoto F, Ito M, Azukizawa H, Kitaba S, Murota H, Itami S, Katayama I, Takeda J, Sano S.
  • Journal Title: J Invest Dermatol. Volume: 133 Issue: 11 Pages: 2555-2565
  • DOI: 10.1038/jid.2013.199
  • Peer Reviewed
• [Journal Article] Cathepsin K Is Involved in Development of Psoriasis-like Skin Lesions through TLR-Dependent Th17 Activation. (2013)
  • Author(s): Hirai T, Kanda T, Sato K, Takaishi M, Nakajima K, Yamamoto M, Kamijima R, Digiovanni J, Sano S.
  • Journal Title: J Immunol Volume: 190(9) Issue: 9 Pages: 4805-11
  • DOI: 10.4049/jimmunol.1200901
  • Peer Reviewed
• [Journal Article] Clear association between serum levels of adipokines and T-helper 17-related cytokines in patients with psoriasis. (2013)
  • Author(s): Nakajima H, Nakajima K, Tarutani M, Sano S.
  • Journal Title: Clin Exp Dermatol. Volume: 38(1) Issue: 1 Pages: 66-70
  • DOI: 10.1111/j.1365-2230.2012.04465.x
  • Peer Reviewed
• [Journal Article] Topical tacrolimus treatment does not facilitate photocarcinogenesis incancer-prone mice. (2012)
  • Author(s): Shiga T, Yokogawa M, Nakajima K, Kitagawa C, Tarutani M, Kumagai N, Sano S.
  • Journal Title: J Dermatol Sci. Volume: 68(2) Issue: 2 Pages: 112-5
  • DOI: 10.1016/j.jdermsci.2012.08.005
  • Peer Reviewed
• [Journal Article] Positive link between STAT3 activation and Th17 cell infiltration to the lesional skin in vitiligo vulgaris. (2012)
  • Author(s): Tanemura A, Kotobuki Y, Itoi S, Takata T, Sano S, Katayama I.
  • Journal Title: J Dermatol Sci. Volume: 67(3) Issue: 3 Pages: 207-9
  • DOI: 10.1016/j.jdermsci.2012.06.010
  • Peer Reviewed
• [Journal Article] GPHR-dependent functions of the Golgi apparatus are essential for the formation of lamellar granules and the skin barrier. (2012)
  • Author(s): Tarutani M, Nakajima K, Uchida Y, Takaishi M, Goto-Inoue N, Ikawa M, Setou M, Kinoshita T, Elias PM, Sano S, Maeda Y
  • Journal Title: J Invest Dermatol. Volume: 132(8) Pages: 2019-25
  • Peer Reviewed
• [Journal Article] Imiquimod attenuates the growth of UVB-induced SCC in mice through Th1/Th17 cells. (2012)
  • Author(s): Yokogawa M, Takaishi M, Nakajima K, Kamijima R, Digiovanni J, Sano S.
  • Journal Title: Mol Carcinog. Volume: (Epub ahead of print) Issue: 10 Pages: 760-769
  • DOI: 10.1002/mc.21901
  • Peer Reviewed
• [Journal Article] Sebaceous glands as the primary target of EGFR-inhibitors in the development of papulopustular eruption. (2012)
  • Author(s): Takata T, Tarutani M, Zouboulis CC, Sano S.
  • Journal Title: J Dermatol Sci. Volume: 66(2) Issue: 2 Pages: 165-8
  • DOI: 10.1016/j.jdermsci.2012.02.012
  • Peer Reviewed
• [Journal Article] Attenuation of psoriasis-like skin lesion in a mouse model by topical treatment with indirubin and its derivative E804. (2012)
  • Author(s): Miyoshi K, Takaishi M, Digiovanni J, Sano S.
  • Journal Title: J Dermatol Sci. Volume: 65(1) Issue: 1 Pages: 70-2
  • DOI: 10.1016/j.jdermsci.2011.10.001
  • Peer Reviewed
• [Journal Article] GPHR-dependent functions of the Golgi apparatus are essential for the formation of lamellar granules and the skin (2012)
  • Author(s): Tarutani M, et al.
  • Journal Title: J Invest Dermatol Volume: 132 Issue: 8 Pages: 2019-2025
  • DOI: 10.1038/jid.2012.100
  • Peer Reviewed
• [Journal Article] FDG PET/CT is a powerful tool for detecting subclinical arthritis in patients with psoriatic arthritis and/or psoriasis vulgaris. (2011)
  • Author(s): Takata T, Taniguchi Y, Ohnishi T, Kohsaki S, Nogami M, Nakajima H, Kumon Y, Terada Y, Ogawa Y, Tarutani M, Sano S.
  • Journal Title: J Dermatol Sci. Volume: 64(2) Issue: 2 Pages: 144-7
  • DOI: 10.1016/j.jdermsci.2011.08.002
  • Peer Reviewed
• [Journal Article] Kinetics of circulating Th17 cytokines and adipokines in psoriasis patients (2011)
  • Author(s): Nakajima H, Nakajima K, et al
  • Journal Title: Archives of Dermatological Research Volume: 303 Issue: 6 Pages: 451-455
  • DOI: 10.1007/s00403-011-1159-3
  • Peer Reviewed
• [Journal Article] Altered lipid profiles in the stratum corneum of Sjogren-Larsson syndrome. (2011)
  • Author(s): Nakajima K, Sano S, Uchida Y, Akiyama M, Morita Y, Shimizu H.
  • Journal Title: J Dermatol Sci Volume: 63(1) Issue: 1 Pages: 64-6
  • DOI: 10.1016/j.jdermsci.2011.03.009
  • NAID: 10030891977
  • Peer Reviewed
• [Journal Article] Distinct roles of IL-23 and IL-17 in the development of psoriasis-like lesions in a mouse model. (2011)
  • Author(s): Nakajima K, Kanda T, Takaishi M, Shiga T, Miyoshi K, Nakajima H, Kamijima R, Tarutani M, Benson JM, Elloso MM, Gutshall LL, Naso MF, Iwakura Y, DiGiovanni J, Sano S.
  • Journal Title: J Immunol. Volume: 186(7) Issue: 7 Pages: 4481-9
  • DOI: 10.4049/jimmunol.1000148
  • Peer Reviewed
• [Journal Article] Stat3 as a Therapeutic Target for the Treatment of Psoriasis : A Clinical Feasibility Study with STA-21, a Stat3 Inhibitor (2011)
  • Author(s): Miyoshi K, Takaishi M, Nakajima K, Ikeda M、Kanda T, Tarutani M, Iiyama T, Asao N, DiGiovanni J, Sano S
  • Journal Title: Journal of Investigative Dermatology Volume: Vol.131 Issue: 1 Pages: 105-117
  • DOI: 10.1038/jid.2010.255
  • Peer Reviewed
• [Journal Article] Stat3 as a therapeutic target for the treatment of psoriasis : a clinical feasibility study with STA-21, a Stat3 inhibitor. (2011)
  • Author(s): Miyoshi K, Takaishi M, Nakajima K, Ikeda M, Kanda T, Tarutani M, Iiyama T, Asao N, DiGiovanni J, Sano S.
  • Journal Title: J Invest Dermatol. Volume: 131 Pages: 108-117
  • Peer Reviewed
• [Presentation] 乾癬の新規治療法 (2012)
  • Author(s): 佐野栄紀
  • Organizer: 第42回日本皮膚アレルギー・接触皮膚炎学会総会学術大会
  • Place of Presentation: 軽井沢プリンスホテル(軽井沢町)
  • Year and Date: 2012-07-15
• [Presentation] Involvement of TNF-α converting enzyme in the development of psoriasis-like lesions in K5.Stat3C transgenic mice (2012)
  • Author(s): Sato K, Takaishi M, Tokuoka S, Sano S
  • Organizer: The 42nd Annual ESDR Meeting
  • Place of Presentation: Palazzo del Casino, Venice Lido Congress Centre (Italy)
• [Presentation] Development of psoriasis-like lesions in a mouse model by IL-23-dependent but IL-22-independent. (2011)
  • Author(s): Takaishi M, Nakajima K, Ouyang W, Sano S.
  • Organizer: The 36th Annual Meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: 京都国立国際会館(京都市)
  • Year and Date: 2011-12-09
• [Presentation] Development of psoriasis-like lesions in a mouse model by IL-23-dependent but IL-22-independent signaling (2011)
  • Author(s): Takaishi, M.
  • Organizer: The 37th Annual Meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: 京都国際会館
  • Year and Date: 2011-12-09
• [Presentation] 乾癬マウスモデルにおけるIL-23依存性IL-22非依存性シグナルによる皮疹形成 (2011)
  • Author(s): 高石樹朗
  • Organizer: 第26回日本乾癬学会学術大会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2011-09-10
• [Presentation] IL-23 is essential, but IL-22 is dispensable for the development of psoriasis-like lesions in K5. (2011)
  • Author(s): Takaishi M, Nakajima K, Ouyang W, Sano S.
  • Organizer: Stat3C mice 41st Annual ESDR Meeting
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2011-09-09
• [Presentation] 乾癬マウスモデルにおけるIL-23依存性IL-22非依存性シグナルによる皮疹形成 (2011)
  • Author(s): 高石 樹朗, 中島喜美子, Wenjun Ouyang, 佐野 栄紀.
  • Organizer: 第26回日本乾癬学会学術大会
  • Place of Presentation: 大阪国際会議場(大阪市)
  • Year and Date: 2011-09-09
• [Presentation] IL-23 is essential, but IL-22 is dispensable for the development of psoriasis-like lesions in K5.Stat3C mice (2011)
  • Author(s): Takaishi, M.
  • Organizer: European Society for Dermatological Research, 41st Annual Meeting
  • Place of Presentation: Barcelona International Convension Center (Spain)
  • Year and Date: 2011-09-07
• [Presentation] Possible contribution of IL-22-producing non-T cells to the development of psoriasis-like lesion in a mouse model. (2010)
  • Author(s): Nakajima K, Singa S, Kanda T, Takaishi M, Miyoshi K, Sano S.
  • Organizer: 日本研究皮膚科学会第35回年次学術大会
  • Place of Presentation: 和歌山県立文化会館(和歌山市)
  • Year and Date: 2010-12-04
• [Presentation] K5.Stat3トランスジェニックマウスに生じる乾癬様皮疹におけるPlasmacytoid dendritic cells(PDCs)の関与 (2010)
  • Author(s): 高石 樹朗, 片岡 健, Kaoru Kiguchi, Michal Gilliet、佐野 栄紀、John Digiovanni.
  • Organizer: 第25回日本乾癬学会学術大会
  • Place of Presentation: 宇部全日空ホテル(宇部市)
  • Year and Date: 2010-09-03
• [Presentation] 乾癬におけるindirubinの有効性 (2010)
  • Author(s): 三好研、高石樹朗、佐野栄紀
  • Organizer: 第25回日本乾癬学会学術大会
  • Place of Presentation: 宇部全日空ホテル(宇部市)
  • Year and Date: 2010-09-03
• [Presentation] Distinct roles of IL-23 and IL-17 in the development of psoriasis-like lesion in a mouse model (2010)
  • Author(s): Nakajima K. Kanda T, Takaishi M, Miyoshi K, Benson JM, Elloso MM, Gutshall LL, Naso MF, Iwakura Y, DiGiovanni J, Sano S.
  • Organizer: 14th International congress of immunology
  • Place of Presentation: 神戸ポートピアホテル(神戸市)
  • Year and Date: 2010-08-28
• [Presentation] 表皮特異的Golgi pH regulator欠損マウスのphenotype (2010)
  • Author(s): 樽谷勝仁、中島喜美子、高石樹朗、佐野栄紀、前田裕輔、木下タロウ
  • Organizer: 第25回角化症研究会
  • Place of Presentation: 東京商工会議所(東京都)
  • Year and Date: 2010-07-31
• [Presentation] 皮膚線維芽細胞のコラーゲン合成におけるSmad interacting protein 1(SIP1)の働き (2010)
  • Author(s): 寺石美香、高石樹朗、池田光徳、古川貴久、深田俊幸、下田信治、朝田芳信、佐野栄紀
  • Organizer: 第17回分子皮膚科学フォーラム
  • Place of Presentation: ホテルオークラ福岡(福岡市)
  • Year and Date: 2010-07-09
• [Presentation] 日光角化症におけるイミキモドの抗腫瘍作用:モデルマウスを用いた解析 (2010)
  • Author(s): 横川真紀、志賀建夫、高石樹朗、樽谷勝仁、佐野栄紀
  • Organizer: 第6回加齢皮膚医学研究会・第358回日本皮膚科学会新潟地方会
  • Place of Presentation: 新潟大学有壬記念館(新潟市)
  • Year and Date: 2010-07-03
• [Presentation] Stat3阻害剤であるSTA-21はヒト正常表皮角化細胞とヒト角化細胞由来株細胞の分化を誘導する (2010)
  • Author(s): 高石樹朗、横川真紀、三好研、中島喜美子、John DiGiovanni、佐野栄紀
  • Organizer: 日本組織培養学会 第83回大会
  • Place of Presentation: 岡山大学(岡山市)
  • Year and Date: 2010-05-21
• [Presentation] STA-21, a stat3 inhibitor, induces differentiation of normal human epidermal keratinocytes and human, keratinocyte derived cell lines. (2010)
  • Author(s): Takaishi M, Yokogawa M, Miyoshi K, Nakajima K, DiGiovanni J, Sano S.
  • Organizer: 70th SID 2010 Annual Meeting
  • Place of Presentation: Hilton Atlanta Hotel, Atlanta, U.S.A
  • Year and Date: 2010-05-05
• [Presentation] Role of Smad-interacting protein 1 (SIP1) in collagen synthesis of dermal fibroblasts. (2010)
  • Author(s): Teraishi M, Takaishi M, Ikeda M, Furukwa T, Shimoda S, Asada Y, Sano S.
  • Organizer: SID 2010 Annual Meeting
  • Place of Presentation: Hilton Atlanta Hotel Atlanta, GA
  • Year and Date: 2010-05-05
• [Presentation] Distinct roles of IL-23 and IL-17 in the development of psoriasis-like lesion in a mouse model. (2010)
  • Author(s): Nakajima K, Kanda T, Takaishi M, Miyoshi K, Benson JM, Elloso MM, Iwakura Y, DiGiovanni J, Sano S.
  • Organizer: SID 2010 Annual Meeting
  • Place of Presentation: Hilton Atlanta Hotel Atlanta, GA
  • Year and Date: 2010-05-05
• [Presentation] STA-21, a stat3 inhibitor, induces differentiation of normal human epidermal keratinocytes and human keratinocyte derived cell lines. (2010)
  • Author(s): Takaishi M, Yokogawa M, Miyoshi K, Nakajima K, DiGiovanni J, Sano S.
  • Organizer: SID 2010 Annual Meeting
  • Place of Presentation: Hilton Atlanta Hotel Atlanta, GA
  • Year and Date: 2010-05-05
• [Presentation] Stat3をターゲットとした新規乾癬治療法の開発 (2010)
  • Author(s): 三好研、中島喜美子、高石樹朗、佐野栄紀
  • Organizer: 第109回日本皮膚科学会総会
  • Place of Presentation: 大阪国際会議場(大阪市)
  • Year and Date: 2010-04-17
• [Book] 乾癬, 今日の治療指針2012年版(Vol54). (2012)
  • Author(s): 佐野栄紀
  • Publisher: 医学書院
• [Book] 乾癬の動物モデル(遺伝子改変マウス, 皮膚科臨床アセット10 (2012)
  • Author(s): 佐野栄紀
  • Publisher: 中山書店
• [Book] 悪性内皮細胞腫, 瀧川雅浩他編, 皮膚疾患最新の治療2011-2012 (2011)
  • Author(s): 佐野栄紀
  • Publisher: 南江堂
• [Book] 第4節乾癬モデル, 疾患モデルの作製と利用-免疫疾患 (2011)
  • Author(s): 佐野栄紀
  • Publisher: 株式会社エル・アイ・シー
• [Book] 魚鱗癬, 飯塚一編, 今日の治療指針2010年版 (Vol.52) (2010)
  • Author(s): 佐野栄紀
  • Total Pages: 967
  • Publisher: 医学書院
• [Patent(Industrial Property Rights)] 膠原病の病態モデル動物、当該病態モデル動物の作製方法、及び当該病態モデル動物のスクリーニング方法 (2012)
  • Inventor(s): 佐野 栄紀,横川 真紀,高石 樹朗
  • Industrial Property Rights Holder: 国立大学法人高知大学
  • Industrial Property Number: 2012-074752
  • Filing Date: 2012-03-28