Investigation of Langerhans cell stimulatory molecule and its application in skin disease therapy

• Project/Area Number: 17209039
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dermatology
• Research Institution: The University of Tokyo
• Principal Investigator: TAMAKI Kunihiko The University of Tokyo, 医学部・附属病院, 教授 (30010432)
• Co-Investigator(Kenkyū-buntansha): ASAHINA Akihiko 東京大学, 医学部・附属病院, 助教授 (50202601) ; KOMINE Mayumi 東京大学, 医学部・附属病院, 講師 (00282632) ; WATANABE Takahiro 東京大学, 医学部・附属病院, 講師 (30280960) ; TADA Yayoi 東京大学, 医学部・附属病院, 助教 (00334409)
• Project Period (FY): 2005 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥49,530,000 (Direct Cost: ¥38,100,000、Indirect Cost: ¥11,430,000); Fiscal Year 2008: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000); Fiscal Year 2007: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000); Fiscal Year 2006: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000); Fiscal Year 2005: ¥20,670,000 (Direct Cost: ¥15,900,000、Indirect Cost: ¥4,770,000)
• Keywords: ランゲルハンス細胞 / 樹状細胞 / 共刺激分子 / 抗原提示 / 活性化

Research Abstract

樹状細胞の成熟を促進する新規遺伝子(GeneA(仮))をマウスランゲルハンス細胞(LC)を用いたcDNAサブトラクション法により見出した。さらにGeneA がCD40の発現を促進し、樹状細胞からのIL-12産生を促進する事により、Th1系反応の誘導に寄与する可能性が示唆された。今後、腫瘍免疫や初期免疫の誘導にGeneAを応用する可能性について引き続き検討して行く。

Research Products

• [Journal Article] CCL27-transgenic mice show enhanced contact hypersensitivity to Th2, but not Th1 stimuli (2008)
  • Author(s): Kagami S, Saeki H, Tsunemi Y, Nakamura K, Kuwano Y, Komine M, Nakayama T, Yoshie O, Tamaki K
  • Journal Title: Eur J Immunol 38巻 Pages: 647-657
  • Peer Reviewed
• [Journal Article] CCL27-transgenic mice show enhanced contact hypersensitivity to Th2, but not Th1 stimuli (2008)
  • Author(s): kagami S., Tamaki K. et al.
  • Journal Title: Eur J Immunol. 38 Pages: 647-657
  • Peer Reviewed
• [Journal Article] Role of TARC/CCL17 and CTACK/CCL27 in thepathogenesis of atopic dermatitis (2008)
  • Author(s): Saeki H., Tamaki K.
  • Journal Title: Curr Immunol Rev. 4 Pages: 221-220
  • Peer Reviewed
• [Journal Article] CCR4 and CCR10 are expressed on epidermal keratinocytes and are involved in cutaneous immune reaction (2008)
  • Author(s): Fujimoto S., Tamaki K. et al.
  • Journal Title: Cytokine 44 Pages: 172-178
  • Peer Reviewed
• [Journal Article] CD19 expression in B cells is important for suppression of contact hypersensitivity (2007)
  • Author(s): Watanabe R, Fujimoto M, Ishiura N, Kuwano Y, Nakashima H, Yazawa N, Okochi H, Sato S, Tedder TF, Tamaki K.
  • Journal Title: Am J Pathol 171巻 Pages: 560-570
  • Peer Reviewed
• [Journal Article] The direct action of 1alpha,25(OH)2-vitamin D3 on purified mouse Langerhans cells (2007)
  • Author(s): Fujita H, Asahina A, Komine M, Tamaki K.
  • Journal Title: Cell Immunol 245巻 Pages: 70-79
  • Peer Reviewed
• [Journal Article] Involvement of the constitutive complex formation of c-Ski/SnoN with Smads in the impaired negative feedback regulation of transforming growth factor beta signaling in scleroderma fibroblasts (2007)
  • Author(s): Jinnin M, Ihn H, Mimura Y, Asano Y, Tamaki K.
  • Journal Title: Arthritis Rheum 56巻 Pages: 1694-1705
  • Peer Reviewed
• [Journal Article] Early inflammatory changes in the "perilesional skin" of psoriatic plaques : is there interaction between dendritic cells and keratinocytes (2007)
  • Author(s): Komine M, Karakawa M, Takekoshi T, Sakurai N, Minatani Y, Mitsui H, Tada Y, Saeki H, Asahina A, Tamaki K.
  • Journal Title: J Invest Dermatol 127巻 Pages: 1915-1922
  • Peer Reviewed
• [Journal Article] CCL17 transgenic mice show an enhanced Th2-type response to both allergic and non-allergic stimuli (2007)
  • Author(s): Tsunemi Y, Saeki H, Nakamura K, Nagakubo D, Nakayama T, Yoshie O, Kagami S, Shimazu K, Kadono T, Sugaya M, Komine M, Matsushima K, Tamaki K
  • Journal Title: Eur J Immunol 36巻 Pages: 2116-2127
  • Peer Reviewed
• [Journal Article] The direct action of lalpha,25(OH)2-vitamin D3 on purified mouse Langerhans cells (2007)
  • Author(s): Fujita H, Tamaki K, et. al.
  • Journal Title: Celular Immunology 245 Pages: 70-79
  • Peer Reviewed
• [Journal Article] CD19 expression in B cells is important for suppression of contact hypersensitivity (2007)
  • Author(s): Watanabe R, Tamaki K, et. al.
  • Journal Title: American Joumal of Pathology 171 Pages: 560-570
  • Peer Reviewed
• [Journal Article] CD83 influences cell-surface MHC class II expression on B cells and otherantien-presenting cells (2007)
  • Author(s): Kuwano Y, Tamaki K, et. al.
  • Journal Title: Intemational Iminunology 19 Pages: 977-992
  • Peer Reviewed
• [Journal Article] The repeat domain of the melanosomal matrix protein PMEL17/GP100 is required for the formation of organellar fibers (2006)
  • Author(s): Hoashi T, Muller J, Vieira WD, Rouzaud F, Kikuchi K, Tamaki K, Hearing VJ
  • Journal Title: J Biol Chem 281巻 Pages: 21198-21208
  • Peer Reviewed
• [Journal Article] Increased expression of integrin alphavbeta5 induces the myofibroblastic differentiation of dermal fibroblasts (2006)
  • Author(s): Asano Y, Ihn H, Yamane K, Jinnin M, Tamaki K
  • Journal Title: Am J Pathol 168巻 Pages: 499-510
  • Peer Reviewed
• [Journal Article] B cell antigen receptor and CD40 differentially regulate CD22 tyrosine phosphorylation (2006)
  • Author(s): Fujimoto M, Kuwano Y, Watanabe R, Asashima N, Nakashima H, Yoshitake S, Okochi H, Tamaki K, Poe JC, Tedder TF, Sato S.
  • Journal Title: J Immunol 176巻 Pages: 873-879
  • Peer Reviewed
• [Journal Article] Rde of Langerhaus cells in cutanecus protectss ismunety : is the appraisal necessary? (2006)
  • Author(s): Asahina A, Tamaki K
  • Journal Title: J Dermotol Sci 44(1) Pages: 1-9
• [Journal Article] Ligation of E-cadheirs malecules on muie rasident Layuks cells inlinbids their maturation and chenhis prodution (2006)
  • Author(s): Fujita H, Asahina A, Tamaki K
  • Journal Title: J Dermatol Sci 43(2) Pages: 152-5
• [Journal Article] CCL17 trausgenic mice show an enhancesh Th2-type response to bath allergic and non-allargie stinuli (2006)
  • Author(s): Tsunemi Y, Tamaki K et al.
  • Journal Title: Ew J Emmurol 36(8) Pages: 2116-27
• [Journal Article] Increased expression of integrin alpha(v)beta3 contributes to the establishment of autocrine TGF-beta signaling in scleroderma fibroblasts (2005)
  • Author(s): Asano Y, Ihn H, Yamane K, Jinnin M, Mimura Y, Tamaki K
  • Journal Title: J Immunol 175巻 Pages: 7708-7718
  • Peer Reviewed
• [Journal Article] Differential production of Th1- and Th2-type chemokines by mouse Langerhans cells and splenic dendritic cells. (2005)
  • Author(s): Fujita H, Asahina A, (omission), Tamaki K
  • Journal Title: J Invest Dermatol 124(2) Pages: 343-350
• [Journal Article] Type I interferons inhibit maturation and activation of mouse Langerhans cells. (2005)
  • Author(s): Fujita H, Asahina A, Tada Y, Fujiwara H, Tamaki K
  • Journal Title: J Invest Dermatol 125(1) Pages: 126-133
• [Journal Article] Mechanism of thymus- and activation-regulated chemokine (TARC)/CCL17 production and its modulation by roxithromycin. (2005)
  • Author(s): Komine M, (omission), Tamaki K
  • Journal Title: J Invest Dermatol 125(3) Pages: 491-498
• [Journal Article] Interleukin-4 and interleukin-13 enhance CCL26 production in a human keratinocyte cell line, HaCaT cells. (2005)
  • Author(s): Kagami S, Saeki H, Komine M, (omission), Asahina A, Tamaki K
  • Journal Title: Clin Exp Immunol 141(3) Pages: 459-466
• [Journal Article] Characterization and localization of side population cells in mouse skin. (2005)
  • Author(s): Yano S, (omission), Tamaki K, Okochi H
  • Journal Title: Stem Cells 23(6) Pages: 834-841
• [Journal Article] Platelet derived growth factor induced tenascin-C transcription is phosphoinositide 3-kinase/Akt-dependent and mediated by Ets family transcription factors. (2005)
  • Author(s): Jinnin M, (omission), Tamaki K
  • Journal Title: J Cell Physiol 206(3) Pages: 718-727
• [Presentation] 特別講演:尿酸と皮膚疾患 (2008)
  • Author(s): 玉置 邦彦
  • Organizer: 日本皮膚科学会西部支部学術大会
  • Place of Presentation: 福岡
  • Year and Date: 2008-10-18
• [Presentation] Invited lecture : Langerhans cells and Toll-like receptors (2007)
  • Author(s): Tamaki K
  • Organizer: 10^<th> International Workshop on Langerhans cells
  • Place of Presentation: Bern, Switzerland
• [Presentation] Symposium : Basic and Clinical Allergology (2007)
  • Author(s): Tamaki K
  • Organizer: World Congress of Dermatology
  • Place of Presentation: Buenos Aires Argentina