The treatment for cedar pollinosis and atopic dermatitis by the local induction of IL-10

• Project/Area Number: 23591643
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Mie University
• Principal Investigator: Yamanaka Keiichi 三重大学, 医学(系)研究科(研究院), 准教授 (70314135)
• Co-Investigator(Kenkyū-buntansha): 水谷 仁 三重大学, 医学(系)研究科(研究院), 教授 (30115737)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 花粉症 / アレルギー / アトピー性皮膚炎 / IL-10 / IL-10産生型抑制性T細胞 / パラインフルエンザウイルス / 免疫療法 / スギ花粉症

Outline of Final Research Achievements

The major goal of this proposal is to investigate when and where IL-10 is produced by repeated Cry j1 and Cry j2 challenge. We had analyzed IL-10 expression using IL-10tm1Flv/J mice in which the cells express GFP when they produce IL-10.

Research Products

• [Journal Article] Continuous high-dose antigen exposure preferentially induces IL-10, but intermittent antigen exposure induces IL-4. (2014)
  • Author(s): Yamanaka K, Nakanishi T, Watanabe J, Kondo M, Yamagiwa A, Gabazza EC, Mizutani H.
  • Journal Title: Exp Dermatol. Volume: 23 Issue: 1 Pages: 63-65
  • DOI: 10.1111/exd.12295
  • Peer Reviewed
• [Journal Article] Novel acoustic evaluation system for scratching behavior in itching dermatitis: Rapid and accurate analysis for nocturnal scratching of atopic dermatitis patients. (2014)
  • Author(s): Noro Y, Omoto Y, Umeda K, Tanaka F, Shiratsuka Y, Yamada T, Isoda K, Matsubara K, Yamanaka K, Gabazza EC, Nishikawa M, Mizutani H.
  • Journal Title: J Dermatol. Volume: 41 Issue: 3 Pages: 233-238
  • DOI: 10.1111/1346-8138.12405
  • Peer Reviewed
• [Journal Article] CD8+ T cell granzyme B activates keratinocyte endogenous IL-18. (2014)
  • Author(s): Akeda T, Yamanaka K, Tsuda K, Omoto Y, Gabazza EC, Mizutani H.
  • Journal Title: Arch Dermatol Res. Volume: 306 Issue: 2 Pages: 125-130
  • DOI: 10.1007/s00403-013-1382-1
  • Peer Reviewed
• [Journal Article] Intranasally administered antigen 85B gene vaccine in non-replicating human Parainfluenza type 2 virus vector ameliorates mouse atopic dermatitis. (2013)
  • Author(s): Kitagawa H, Kawano M, Yamanaka K, Kakeda M, Tsuda K, Inada H, Yoneda M, Sakaguchi T, Nigi A, Nishimura K, Komada H, Tsurudome M, Yasutomi Y, Nosaka T, Mizutani H.
  • Journal Title: PLoS One. Volume: 8 Issue: 7 Pages: 66614-66614
  • DOI: 10.1371/journal.pone.0066614
  • Peer Reviewed
• [Journal Article] Mutant interleukin-4/13 signaling blockade successfully suppresses acute phase inflammation. (2013)
  • Author(s): Nakanishi T, Yamanaka K, Kakeda M, Tsuda K, Mizutani H.
  • Journal Title: Arch Dermatol Res. Volume: 305 Issue: 3 Pages: 241-247
  • DOI: 10.1007/s00403-012-1302-9
  • Peer Reviewed
• [Journal Article] Ustekinumab improves psoriasis without altering T cell cytokine production, differentiation, and T cell receptor repertoire diversity (2012)
  • Author(s): Tsuda K, Yamanaka K, Kondo M, Matsubara K, Sasaki R, Tomimoto H, Gabazza EC, Mizutani H.
  • Journal Title: PLoS One Volume: 7 Issue: 12 Pages: 51819-51819
  • DOI: 10.1371/journal.pone.0051819
  • Peer Reviewed
• [Journal Article] Calcineurin inhibitors suppress cytokine production from memory T cells and differentiation of naive T cells into cytokine-producing mature T cells. (2012)
  • Author(s): Tsuda K, Yamanaka K, Kitagawa H, Akeda T, Naka M, Niwa K, Nakanishi T, Kakeda M, Gabazza EC, Mizutani H.
  • Journal Title: PLoS One Volume: 7 Issue: 2 Pages: 31465-31465
  • DOI: 10.1371/journal.pone.0031465
  • Peer Reviewed
• [Journal Article] Heat-killed bacillus Calmette-Guerin and Mycobacterium kansasii antigen 85B combined vaccination ameliorates dermatitis in a mouse model of atopic dermatitis by inducing regulatory T cells. (2012)
  • Author(s): Kakeda M, Yamanaka K, Kitagawa H, Tsuda K, Akeda T, Kurokawa I, Gabazza EC, Mizutani H.
  • Journal Title: Br J Dermatol. Volume: 166 Pages: 953-63
  • Peer Reviewed
• [Journal Article] 見えぬ免疫を見えるがごとく説明する (2012)
  • Author(s): 山中恵一
  • Journal Title: 臨床皮膚科 Volume: 66 Pages: 127-127
  • Peer Reviewed
• [Journal Article] Heat-killed BCG and Mycobacterium kansasii Ag85B combined vaccination ameliorates dermatitis in a mouse model of atopic dermatitis by inducing regulatory T cells (2012)
  • Author(s): Kakeda M, Yamanaka K, Mizutani H, et al
  • Journal Title: Br J Dermatol Volume: 1 Issue: 5 Pages: 1-1
  • DOI: 10.1111/j.1365-2133.2011.10763.x
  • Peer Reviewed
• [Journal Article] Calcineurin inhibitors suppress cytokine production from memory T cells and differentiation of naïve T cells into cytokine-producing mature T cells (2012)
  • Author(s): K Tsuda, K Yamanaka, H Kitagawa, T Akeda, M Naka, K Niwa, T Nakanishi, M Kakeda, EC Gabazza, and H Mizutani
  • Journal Title: PLoS ONE Volume: 7 Pages: 31465-31465
  • Peer Reviewed
• [Journal Article] Propionibacterium acnes vaccination induces regulatory T cells and Th1 immune responses and improves mouse atopic dermatitis (2011)
  • Author(s): H. Kitagawa, K. Yamanaka, M. Kakeda, H. Inada, Y. Imai, E. C. Gabazza, I. Kurokawa and H. Mizutani
  • Journal Title: Exp Dermatol Volume: 20 Issue: 2 Pages: 157-158
  • DOI: 10.1111/j.1600-0625.2010.01180.x
  • Peer Reviewed
• [Journal Article] "The Role of Cytokines /Chemokines in the Pathogenesis of Atopic Dermatitis" (2011)
  • Author(s): K. Yamanaka and H. Mizutani
  • Journal Title: CURRENT PROBLEMS IN DERMATOLOGY Volume: 41 Pages: 80-92
  • Peer Reviewed
• [Journal Article] SLIT Improves Cedar Pollinosis by Restoring IL-10 Production from Tr1 and Monocytes~ IL-10 Productivity Is Critical for Becoming Allergic ~ (2011)
  • Author(s): K. Yamanaka, A. Yuta, M. Kakeda, H. Kitagawa, H. Ogihara, E. C. Gabazza, K. Okubo, I. Kurokawa, K. Takeuchi and H. Mizutani
  • Journal Title: Allergol Int Volume: 60 Pages: 45-51
  • NAID: 10031143298
  • Peer Reviewed
• [Journal Article] High scatter T cells (THS): a reliable biomarker for malignant T cells in cutaneous T cell lymphoma (2011)
  • Author(s): Rachael A Clark, Jeffrey B Shackelton, Rei Watanabe, Adam Calarese, Kei-ichi Yamanaka, James J Campbell, Jessica Teague, Helen Kuo, DirkJan Hijnen, and Thomas S Kupper
  • Journal Title: Blood Volume: 117 Pages: 1966-1976
  • Peer Reviewed
• [Journal Article] Intratumoral Injection of Propionibacterium acnes Suppresses Malignant Melanoma by Enhancing Th1 Immune Responses. (2011)
  • Author(s): Tsuda K, Yamanaka K, Linan W, Miyahara Y, Akeda T, Nakanishi T, Kitagawa H, Kakeda M, Kurokawa I, Shiku H, Gabazza EC, Mizutani H.
  • Journal Title: PLoS ONE Volume: 6 Pages: 29020-29020
  • Peer Reviewed
• [Presentation] Atopic dermatitis and immune-modulation (2014)
  • Author(s): Keiichi Yamanaka
  • Organizer: The 24th Annual Meeting of the Korean Society for Investigative Dermatology
  • Place of Presentation: South Korea
  • Invited
• [Presentation] アレルギーに関する研究成果を診療に生かす (2014)
  • Author(s): 山中恵一
  • Organizer: 第77回日本皮膚科学会東京支部学術大会
  • Place of Presentation: 東京
  • Invited
• [Presentation] Atopic dermatitis as a potential driver of systemic inflammation; IL-1 released from inflamed skin keratinocytes Causes arteriosclerosis, amyloidosis and Impaired lipid fat remodeling (2013)
  • Author(s): Keiichi YAMANAKA, Motomu SHIMAOKA, Hitoshi MIZUTANI
  • Organizer: 第42回日本免疫学会
  • Place of Presentation: 千葉県幕張市
• [Presentation] かゆみの治療戦略 (2013)
  • Author(s): 山中恵一
  • Organizer: 第43 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: 金沢市
  • Invited
• [Presentation] アトピー性皮膚炎の新しい話題～どうしても掻破を止めたい その理由 (2013)
  • Author(s): 山中恵一
  • Organizer: 第112回 H25年度 日本皮膚科学会総会
  • Place of Presentation: 横浜市
  • Invited
• [Presentation] Calcineurin inhibitors suppress cytokine production from memory T cells and differentiation of naive T cells into cytokine-producing mature T cells. (2012)
  • Author(s): K. Yamanaka, K. Tsuda, H. Kitagawa, T. Akeda, M. Naka, K. Niwa, T. Nakanishi, M. Kakeda, H. Mizutani
  • Organizer: 75th Annual Meeting of the Society for Investigative Dermatology
  • Place of Presentation: Raleigh,USA
• [Presentation] 生物学的製剤のサイトカイン産生能・Ｔ細胞免疫に与える影響 (2012)
  • Author(s): 山中恵一, 津田憲志郎, 松原きみ子, 近藤誠, 明田智子, 水谷仁
  • Organizer: 第27回日本乾癬学会学術大会
  • Place of Presentation: 新潟市
• [Presentation] Ustekinumab improved psoriasis without altering T cell immunity:cytokine production,differentiation,T cell receptor repertoire diversity (2012)
  • Author(s): K. Yamanaka, K. Tsuda, K. Matsubara, M. Kondo, H. Mizutani
  • Organizer: The 37tn Annual Meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: Okinawa
• [Presentation] Continuous antigen exposure elicits increased IL-10 production, but intermittent antigen exposure induces IL-4 production (2011)
  • Author(s): K.Yamanaka. Tsuda, T. Akeda, T. Nakanishi, H. Kitagawa, M. Kakeda and H. Mizutani
  • Organizer: 74th Annual Meeting of the Society for Investigative Dermatology
  • Place of Presentation: Arizona, USA
• [Presentation] Low IL-10 Production to Allergen is an underlying defect in allergic disease (2011)
  • Author(s): K. Yamanaka, A. Yuta, M. Kakeda, H. Kitagawa, K. Tsuda, T. Akeda, I. Kurokawa, K. Takeuchi, H. Mizutani
  • Organizer: 22nd World Congress of Dermatology
  • Place of Presentation: Seoul, Korea