The induction of antigen specific regulatory T cells in Japanese cedar allergy

• Project/Area Number: 20591342
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dermatology
• Research Institution: Mie University
• Principal Investigator: YAMANAKA Keiichi Mie University, 医学部附属病院, 講師 (70314135)
• Co-Investigator(Kenkyū-buntansha): MIZUTANI Hitoshi 三重大学, 大学院・医学系研究科, 教授 (30115737)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2010: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000); Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2008: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
• Keywords: IL-10 / 花粉症 / 抑制性T細胞 / 減感作療法

Research Abstract

Allergen-specific immunotherapy (SIT) is currently used for several allergic disorders, and we have investigated the induction of IL-10-producing regulatory T cells (Tr1) and IL-10 producing monocytes by SIT. CD4 T cells and monocytes from SIT group produced high levels of IL-10, suggesting that the induction of IL-10 is essential for T cell tolerance. The low productivity of IL-10 may be closely related with sensitivity to multiple allergens, and resistance to allergic diseases.

Research Products

• [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, et al.
  • Journal Title: Allergology International Volume: 60 Pages: 45-51
  • Peer Reviewed
• [Journal Article] High scatter T cells (T_<HS>) : a reliable biomarker for malignant T cells in cutaneous T cell lymphoma (2011)
  • Author(s): RA.Clark, K.Yamanaka, et al
  • Journal Title: Blood Volume: 117 Pages: 1966-1976
  • Peer Reviewed
• [Journal Article] Possible case for false-positive reaction in serum 5-S-cysteinyldopa levels in a patient with malignant melanoma by ingestion of Agaricus blazei Murrill extract. (2011)
  • Author(s): H.Konishi, K.Yamanaka, et al
  • Journal Title: J Dermatol Volume: 37 Pages: 773-775
  • NAID: 10027067133
  • 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, et al
  • Journal Title: Experimental Dermatology Volume: 20 Pages: 157-158
  • Peer Reviewed
• [Journal Article] Topical treatment with incision and antiseptic may prevent the severity of Japan spotted fever. (2010)
  • Author(s): M.Kondo, I.Kurokawa, K.Yamanaka, S.Akachi, M.Nishii
  • Journal Title: J Dermatol 37 Pages: 835-836
  • Peer Reviewed
• [Journal Article] Japanese Spotted Fever with acute hepatic failure : Was it associated with Epstein-Barr virus? (2010)
  • Author(s): M.Kondo, I.Kurokawa, K.Yamanaka, S.Akachi, M.Nishii
  • Journal Title: Int J Dermatol 49 Pages: 1403-1405
  • Peer Reviewed
• [Journal Article] Immunohistochemical study of cytokeratin expression in nevus sebaceous (2010)
  • Author(s): I.Kurokawa, K.Nishimura, K.Yamanaka, K.Isoda, Y.Taniguchi, D.Tsuruta, A.Tsubura, H.Mizutani
  • Journal Title: The International Society of Dermatology 49 Pages: 402-405
  • Peer Reviewed
• [Journal Article] Possible case for false-positive reaction in serum 5-S-cysteinyldopa levels in a patient with malignant melanoma by ingestion of Agaricus blazei Murrill extract. (2010)
  • Author(s): H.Konishi, K.Yamanaka H.Mizutani
  • Journal Title: J Dermatol 37 Pages: 773-775
  • NAID: 10027067133
  • Peer Reviewed
• [Journal Article] Granzyme B is a novel interleukin-18 converting enzyme (2010)
  • Author(s): Y.Omoto, K.Yamanaka, K.Tokime, S.Kitano, M.Kakeda, T.Akeda, I.Kurokawa, E.Gabazza, H.Tsutusi, N.Katayama, K.Yamanishi, K.Nakanishi, H.Mizutani
  • Journal Title: Journal of Dermatological Science 59 Pages: 129-135
  • NAID: 10027401986
  • Peer Reviewed
• [Journal Article] Restoration of peripheral blood T cell repertoire complexity during remission in advanced cutaneous T cell lymphoma. (2010)
  • Author(s): K.Yamanaka, RC.Fuhlbrigge, H.Mizutani, TS.Kupper
  • Journal Title: Arch Dermatol Res 302 Pages: 453-459
  • Peer Reviewed
• [Journal Article] 1,24-Dihydroxyvitamin D(3) (tacalcitol) prevents skin T-cell infiltration. (2010)
  • Author(s): K.Yamanaka, M.Kakeda, H.Kitagawa, K.Tsuda, T.Akeda, I.Kurokawa, E.Gabazza, TS.Kupper, H.Mizutani
  • Journal Title: Br J Dennatol 162 Pages: 1206-1215
  • Peer Reviewed
• [Journal Article] Epidermal cyst with pilomatricoma (follicular hybrid cyst): immunohistochemical study with epithelial keratins and filaggrin. (2010)
  • Author(s): N.Tsuji, I.Kurokawa, K.Tokime, Y.Omoto, Y.Senba, K.Habe, K.Yamanaka, K.Isoda, A.Tsubura, H.Mizutani
  • Journal Title: J Dennatol 37 Pages: 922-925
  • NAID: 10027572476
  • Peer Reviewed
• [Journal Article] Primary cutaneous apocrine carcinoma arising within a congenital nevus : Keratins and filaggrin expression suggesting differentiation into the secretory cells of apocrine glands (2010)
  • Author(s): Y.Senba, I.Kurokawa, K.Tokime, K.Babe, K.Isoda, K.Yamanaka, A.Tsubura, H.
  • Journal Title: Mizutani ONCOLOGY LETTERS 1 Pages: 413-416
  • Peer Reviewed
• [Journal Article] Treatment of cloth with a fabric softener ameliorates skin dryness (2010)
  • Author(s): K.Isoda, Y.Takagi, T.Kitahara, Y.Sane, I.Sugano, K.Umeda-Togami, K.Umeda, K.Yamanaka, T.Yamada, H.Mizutani
  • Journal Title: Journal of Dermatology 37 Pages: 1-8
  • NAID: 10031147068
  • Peer Reviewed
• [Journal Article] 1,24-Dihydroxyvitamin D(3) (tacalcitol) prevents skin T-cell infiltration. (2010)
  • Author(s): K.Yamanaka, et al.
  • Journal Title: Br J Dermatol Volume: 162 Pages: 1206-1215
  • Peer Reviewed
• [Journal Article] Restoration of peripheral blood T cell repertoire complexity during remission in advanced cutaneous T cell lymphoma. (2010)
  • Author(s): K.Yamanaka, et al.
  • Journal Title: Arch Dermatol Res Volume: 302 Pages: 453-459
  • Peer Reviewed
• [Journal Article] Granzyme B is a novel interleukin-18 converting enzyme (2010)
  • Author(s): Y.Omoto, K.Yamanaka, et al
  • Journal Title: Journal of Dermatological Science Volume: 59 Pages: 129-135
  • NAID: 10027401986
  • Peer Reviewed
• [Journal Article] Immunohistochemical study of cytokeratin expression in nevus sebaceous (2010)
  • Author(s): I.Kurokawa, K.Yamanaka, et al
  • Journal Title: The International Society of Dermatology Volume: 49 Pages: 402-405
  • Peer Reviewed
• [Journal Article] Japanese Spotted Fever with acute hepatic failure : Was it associated with Epstein-Barr virus? (2010)
  • Author(s): M.Kondo, K.Yamanaka, et al
  • Journal Title: Int J Dermatol Volume: 49 Pages: 1403-1405
  • Peer Reviewed
• [Journal Article] Topical treatment with incision and antiseptic may prevent the severity of Japan spotted fever. (2010)
  • Author(s): M.Kondo, K.Yamanaka, et al
  • Journal Title: J Dermatol Volume: 37 Pages: 835-836
  • Peer Reviewed
• [Journal Article] Treatment of cloth with a fabric softener ameliorates skin dryness (2010)
  • Author(s): K.Isoda, K.Yamanaka, et al
  • Journal Title: Journal of Dermatology Volume: 37 Pages: 1-8
  • NAID: 10031147068
  • Peer Reviewed
• [Journal Article] Primary cutaneous apocrine carcinoma arising within a congenital nevus : Keratins and filaggrin expression suggesting differentiation into the secretory cells of apocrine glands (2010)
  • Author(s): Y.Senba, K.Yamanaka, et al
  • Journal Title: ONCOLOGY LETTERS Volume: 1 Pages: 413-416
  • Peer Reviewed
• [Journal Article] Epidermal cyst with pilomatricoma (follicular hybrid cyst) : immunohistochemical study with epithelial keratins and filaggrin. (2010)
  • Author(s): N.Tsuji, K.Yamanaka, et al
  • Journal Title: J Dermatol Volume: 37 Pages: 922-922
  • Peer Reviewed
• [Journal Article] Pilomatricoma can differentiate not only towards hair matrix and hair cortex,but also follicular infundibulum,outer root sheath and hair bulge. (2009)
  • Author(s): I.Kurokawa, K.Yamanaka, Y.Seuba, H.Sugisaki, A.Tsubura, T.Kimura, H.Mizutani
  • Journal Title: Experimental Dermatology 18(8) Pages: 734-737
  • Peer Reviewed
• [Journal Article] Leg ulcer caused by Mycobacterium ulcerans ssp.shinshuense infection (2009)
  • Author(s): M.Kondo, I.Kurokawa, Y.Ito, K.Yamanaka, T.Yamazaki, H.Mizutani
  • Journal Title: International Journal of Dermatology 48(12) Pages: 1330-1333
  • Peer Reviewed
• [Journal Article] Administration of Ag85B showed therapeutic effects to Th2-type cytokine-mediated acute phase atopic dermatitis by inducing by inducing regulatory T cells (2009)
  • Author(s): H.Mori, K.Yamanaka, K.Matsuo, I.Kuorkawa, Y.Yasutomi, H.Mizutani
  • Journal Title: Arch Dermatol Res 301(2) Pages: 151-157
  • Peer Reviewed
• [Journal Article] A Case of Beau's Lines at Even Intervals and Onycholysis Caused by Chemotherapy (2009)
  • Author(s): T.Morioka, I.Kurokawa, K.Yamanaka, H.Sugisaki, K.Habe, K.Isoda, H.Mizutani
  • Journal Title: The Open Dermatology Journal 3(1) Pages: 16-17
  • Peer Reviewed
• [Journal Article] IL-4/IL-13 antagonist DNA vaccination successfully suppresses Th2 type chronic dermatitis (2009)
  • Author(s): T.Morioka, K.Yamanaka, H.Mori, Y.Omoto, K.Tokime, M.Kakeda, I.Kuorkawa, E.C.Gabazza, A.Tsubura, Y.Yasutomi, H.Mizitani British
  • Journal Title: Journal of Dermatology 160(6) Pages: 1172-1179
  • Peer Reviewed
• [Journal Article] differentiates toward the infmndibulum, sebaceous duct and sebaceous cells : immunohistochemical study of keratins and filaggrin (2009)
  • Author(s): Y.Senba, I.Kurokawa, H.Kitagawa, Y.Omoto, K.Yamanaka, K.Isoda, A.Tsubura, H.Mizutani
  • Journal Title: British Journal of Dermatology 160(2) Pages: 454-456
  • Peer Reviewed
• [Journal Article] Case of creeping disease treated with ivermectin. (2009)
  • Author(s): Y.Senba, K.Tsuda, H.Maruyama, I.Kurokawa, H.Mizutani, Y.Taniguchi
  • Journal Title: Jounrnal of Dermatology 36(2) Pages: 86-89
  • NAID: 10025199874
  • Peer Reviewed
• [Journal Article] Increased Interferon-γ, interleukin-12p40 and IL-8 production in Propionibacterium acnes-treated peripheral blood mononuclear cells from patient with acne vulgaris Host response but not bacterial species is the determinant factor of the disease (2009)
  • Author(s): H.Sugisaki, K.Yamanaka, M.Kakeda, H.Kitagawa, K.Tanaka, K.Watanabe, E.Gabazza, I.Kurokawa, H.Mizutani
  • Journal Title: Journal of Dermatol Science 55(1) Pages: 47-52
  • NAID: 10025334262
  • Peer Reviewed
• [Journal Article] Induction of IL-10-producing regulatory T cells with TCR diversity by epitope-specific immunotherapy in pollinosis. (2009)
  • Author(s): K.Yamanaka, A.Yuta, M.Kakeda, R.Sasaki, H.Kitagawa, E.Gabazza, K.Okubo, I.Kurokawa, H.Mizutani
  • Journal Title: J Allergy Clin Immunol 124(4) Pages: 842-845
• [Journal Article] Induction of IL-10-producing regulatory T cells with TCR diversity by epitope-specific immunotherapy in pollinosis (2009)
  • Author(s): Yamanaka, et, al.
  • Journal Title: J Allergy Clin Immunol. 124 Pages: 842-845
  • Peer Reviewed
• [Journal Article] Pilomatricoma can differentiate not only towards hair matrix and hair cortex, but also follicular infundibulum, outer root sheath and hair bulge (2009)
  • Author(s): Kurokawa, Yamanaka, et, at.
  • Journal Title: Exp Dermatol. 18 Pages: 834-837
  • Peer Reviewed
• [Journal Article] IL-4/IL-13 antagonist DNA vaccination successfully suppresses Th2 type chronic dermatitis (2009)
  • Author(s): Morioka, Yamanaka, et, al.
  • Journal Title: Br J Dermatol. 160 Pages: 1172-1179
  • Peer Reviewed
• [Journal Article] Increased interferon-gamma, interleukin-12p40 and IL-8 production in Propionibacterium acnes-treated peripheral blood mononuclear cells from patient with acne vulgaris : host response but not bacterial species is the determinant factor of the disease (2009)
  • Author(s): Sugisaki, Yamanaka, et, al.
  • Journal Title: J Dermatol Sci. 55 Pages: 47-52
  • Peer Reviewed
• [Journal Article] (2009)
  • Author(s): 山中恵一
  • Journal Title: 炎症再生医学事典(朝倉書店) Pages: 223-226
• [Journal Article] Increasedinterferon-g, interleukin-12 p40 and IL-8 productionin Propionibacterium acnes-treated peripheral blood mononuclear cells from patient with acne vulgaris (2009)
  • Author(s): Sugisaki, Yamanaka, et al
  • Journal Title: Archives Dermatological research (accepted)
  • Peer Reviewed
• [Journal Article] Enhanced production and secretion of glial cell line-derived neurotrophic factor and nerve growth factor from the skin in atopic dermatitis mouse model. (2008)
  • Author(s): Tokime K, Katoh-Semba R, Yamanaka K, Mizoguchi A, Mizutani H.
  • Journal Title: Arch Dermatol Res. Pages: 343-352
  • Peer Reviewed
• [Journal Article] Administration of Ag85B showed therapeutic effects to Th2-type cytokine-mediated acute phase atopic dermatitis by inducing regulatory T cells. (2008)
  • Author(s): Mori H, Yamanaka K, Matsuo K, Kurokawa I, Yasutomi Y, Mizutani H.
  • Journal Title: Arch Dermatol Res.
  • NAID: 120001214874
  • Peer Reviewed
• [Journal Article] Protective role of interleukin-18 against Fas-mediated liver injury. (2008)
  • Author(s): Yamamoto N, Murata K, Yoneda K, Fake H, Yamaguchi Y, Sugimoto K, Shiraki K, Yamanaka K, Mizutani H, Takei Y.
  • Journal Title: Int J Mol Med. 22(1) Pages: 43-48
  • Peer Reviewed
• [Journal Article] Freshly isolated Langerhans cells negatively regulate naive T cell activation in response to peptide antigen through cell-to-cell contact. (2008)
  • Author(s): Imai Y, Hayashi N, Yasuda K, Tsutsui H, Mizutani H, Nakanishi K.
  • Journal Title: J Dermatol Sci. 51(1) Pages: 19-29
  • NAID: 10024119334
  • Peer Reviewed
• [Journal Article] Effect of 14-membered-ring macrolides on production of interleukin-8 mediated by protease-activated receptor 2 in human keratinocytes. (2008)
  • Author(s): Tsuda T, Ishikawa C, Konishi H, Hayashi Y, Nakagawa N, Matsuki M, Mizutani H, Yamanishi K.
  • Journal Title: Antimicrob Agents Chemother. 52(4) Pages: 1538-1541
  • Peer Reviewed
• [Journal Article] Folliculosebaceous cystic hamartoma differentiates toward the infundibulum, sebaceous duct and sebaceous cells : immunohistochemical study of keratins and filaggrin. (2008)
  • Author(s): Senba, Yamanaka, et al
  • Journal Title: Br J Dermatol 160(epub)
  • Peer Reviewed
• [Journal Article] Administration of Ag85B showed therapeutic effects to Th2-type cytokine-mediated acute phase atopic dermatitis by inducing regulatory T cells. (2008)
  • Author(s): Mori, Yamanaka, et al
  • Journal Title: Arch Dermatol Res 301(epub)
  • NAID: 120001214874
  • Peer Reviewed
• [Journal Article] Keratin and filaggrin expression in keratoacanthoma. (2008)
  • Author(s): Ito, Yamanaka, et al
  • Journal Title: J Eur Acad Dermatol Venereol. 252 Pages: 353-355
  • Peer Reviewed
• [Journal Article] Necrobiotic xanthogranuloma with paraproteinemia (2008)
  • Author(s): Ito, Yamanaka, et al
  • Journal Title: J Dtsch Dermatol Ges 6 Pages: 40-43
  • Peer Reviewed
• [Journal Article] Keratin and filaggrin expression in comedonal Darier's diseas
  • Author(s): Kurokawa I, Tsuruta D, Tsubura A, Mizutani H
  • Journal Title: J Dermatol in press
  • Peer Reviewed
• [Journal Article] SLIT improves cedar pollinosis by restoring IL-10 production from TrI and monocytes～IL-10 productivity is critical for becoming allergic～
  • Author(s): K.Yamanaka, A.Yuta, M.Kakeda, H.Kitagawa, H.Ogihara, EC Gabazza, K.Okubo, I.Kurokawa, K.Takeuchi, H.Mizutani
  • Journal Title: Allergology International in press
  • Peer Reviewed
• [Journal Article] High scatter T cells (T_<HS>): a reliable biomarker for malignant T cells in cutaneous T cell lymphoma Rachael A Clark, Jeffrey B Shackelton, Rei Watanabe, Adam Calarese
  • Author(s): Kei-ichi Yamanaka, James J Campbell, Jessica Teague, Helen Kuo, DirkJan Hijnen, Thomas
  • Journal Title: S Kupper Blood in press
  • Peer Reviewed
• [Journal Article] Propionibacterium acnes vaccination induces regulatory T cells and Th1 immune responses and improves mouse atopic dermatitis
  • Author(s): H.Kitagawa, K.Yamanaka, M.Kakeda, H.Inada, Y.Imai, EC.Gabazza, I.Kurokawa, H.Mizutani
  • Journal Title: Experimental Dermatology in press
  • Peer Reviewed
• [Presentation] 花粉症に対する免疫療法とIL-10産生抑制性T細胞の誘導 (2009)
  • Author(s): 山中恵一, 湯田厚司, 欠田成人, 北川敬之, 大久保公裕, 黒川一郎, 水谷仁
  • Organizer: 第59回日本アレルギー学会秋季学術大会
  • Place of Presentation: 秋田市
  • Year and Date: 2009-10-31
• [Presentation] 花粉症に対する免疫療法とIL-10産生抑制性T細胞の誘導 (2009)
  • Author(s): 山中恵一
  • Organizer: 第59回日本アレルギー学会秋期大会
  • Place of Presentation: 秋田市
  • Year and Date: 2009-10-31
• [Presentation] Cutaneous Lymphocyte- Associated Antigen(CLA)とVitaminA and D (2009)
  • Author(s): 山中恵一
  • Organizer: 第41回日本臨床分子形態学会総会・学術集会
  • Place of Presentation: 神戸市
  • Year and Date: 2009-09-04
• [Presentation] 花粉症 に対する免疫療法の意義 (2009)
  • Author(s): 山中恵一
  • Organizer: 箱根カンファレンス
  • Place of Presentation: 東京都
  • Year and Date: 2009-08-23
• [Presentation] 尋常性乾癬の病態と治療 (2009)
  • Author(s): 山中恵一
  • Organizer: 第149回日本皮膚科学会山口地方会(特別講演)
  • Place of Presentation: 宇部市
  • Year and Date: 2009-06-28
• [Presentation] 尋常性乾癬の病態と治療 (2009)
  • Author(s): 山中恵一
  • Organizer: 第149回日本皮膚科学会山口地方会
  • Place of Presentation: 山口市
  • Year and Date: 2009-06-28
• [Presentation] 新しい概念と新規の治療法 (2008)
  • Author(s): 山中恵一
  • Organizer: 第59回日本皮膚科学会中部支部学術大会教育講演尋常性乾癬の病態と治療
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-11
• [Presentation] リウマチ性疾患に対する多角的アプローチ-皮膚科の立場から-最近の症例とongoing project (2008)
  • Author(s): 山中恵一
  • Organizer: 日本リウマチ学会近畿地区学術大会
  • Place of Presentation: 大阪
  • Year and Date: 2008-09-06
• [Presentation] 1, 24-dihydroxyvitamin D_3 (tacalcitol) inhibits allergic contact dermatitis via suppression of cutaneous lymphocyte-associated antigen (CLA) expression (2008)
  • Author(s): Yamanaka, et al
  • Organizer: 国際研究皮膚科学会
  • Place of Presentation: Kyoto
• [Presentation] 菌状息肉症におけるクローンの解析 (2008)
  • Author(s): 山中恵一, 他
  • Organizer: 日本皮膚科学会総会
  • Place of Presentation: 京都
• [Presentation] 尋常性乾癬の病態と治療〜新しい概念と新規の治療法〜 (2008)
  • Author(s): 山中恵一
  • Organizer: 第59回 日本皮膚科学会中部支部学術大会
  • Place of Presentation: 名古屋
• [Book] The Role of Cytokines/Chemokines in the Pathogenesis of Atopic Dermatitis(CURRENT PROBLEMS IN DERMATOLOGY Chpter 14.)(Switzerland)
  • Author(s): K.Yamanaka, H.Mizutani
  • Publisher: Karger Publishers(in press)
• [Book] Regulatory T cells in allergic disorders and immunomodulation(Regulatory T cells Chapter 14.)(INC.New York, USA)
  • Author(s): K.Yamanaka
  • Publisher: NOVA SCIENCE PUBLISHERS(in press)