皮膚ランゲルハンス細胞における抗原提示制御分子の解析

• Project/Area Number: 15790568
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Dermatology
• Research Institution: The University of Tokyo
• Principal Investigator: 渡邊 孝宏 東京大学, 医学部附属病院, 講師 (30280960)
• Project Period (FY): 2003 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,700,000 (Direct Cost: ¥3,700,000); Fiscal Year 2005: ¥500,000 (Direct Cost: ¥500,000); Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000); Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
• Keywords: ランゲルハンス細胞 / 樹状細胞 / マクロファージ / 抗原提示

Research Abstract

平成16年度までに、ランゲルハンス細胞(Langerhans cell, LC)が成熟する際に発現が増強する遺伝子implantation-related RGS2-like protein (AF432916)をクローニングした。リンパ臓器(胸腺、リンパ節、脾臓)、非リンパ臓器(脳、腎臓、肝臓)、樹状細胞(LC,脾臓由来CD11c^+細胞、bone marrow-derived dendritic cell [BMDC])、マクロファージのcell line(J774.1、J774A.1、RAW264)におけるこの遺伝子の発現の変化をreal-time PCRを用いて解析したところ、免疫担当細胞では樹状細胞にこの遺伝子が特異的に発現していること、精製直後のLC、脾臓由来CD11c^+細胞では発現は認められなかったが、BMDCでは精製直後より強い発現がみられること、さらにLC以外の樹状細胞においても成熟に伴い発現が増強することがわかった。次にこの遺伝子にコードされている蛋白のうち、C末端側の18アミノ酸を合成し、ウサギに免疫してポリクローナル抗体を作製した。この抗体を用いてFACSを行い、LCとBMDCでは成熟に伴いAF432916の発現が増強していることを蛋白レベルでも確認した。また、BMDCではデキサメサゾン添加によりAF432916の蛋白発現が抑制されるが、IL-10やTGF-β添加では抑制されないこと、LPS、コルヒチン存在下では蛋白発現が増強することが示された。

Research Products

• [Journal Article] Evaluation of the treatment of port-wine stains with the 595-nm long pulsed dye laser. (2006)
  • Author(s): Asahina A, Watanabe T, Kishi A, Hattori N, Shirai A, et al.
  • Journal Title: J Am Acad Dermatol 54 Pages: 487-493
• [Journal Article] Lymphatic dysfunction in transgenic mice expressing KSHV k-cyclin under the control of the VEGFR-3 promoter. (2005)
  • Author(s): Sugaya M, Watanabe T, Yang A, Starost MF, Kobayashi H, Atkins AM, et al.
  • Journal Title: Blood 105 Pages: 2356-2363
• [Journal Article] Mycosis fungoides associated with intestinal mucosa-associated lymphoid tissue lymphoma. (2005)
  • Author(s): Ohmatu H, Saeki H, Fujita H, Toyoma K, Sugaya M, Asahina A, Matsuda S, Hirai H, Watanabe T, et al.
  • Journal Title: Int J Dermatol 44 Pages: 877-880
• [Journal Article] Focal palmoplantar callosities in non-Herlitz junctional epidermolysis bullosa. (2005)
  • Author(s): Mitsui H, Watanabe T, Komine M, Nakamura H, Shimizu H, Tamaki K.
  • Journal Title: J Am Acad Dermatol 52 Pages: 371-373
• [Journal Article] Lymphatic dysfunction in transgenic mice expressing KSHV k-cyclin under the control of the VEGFR-3 promoter. (2005)
  • Author(s): Sugaya M, Watanabe T, Yang A, Starost MF, Kobayashi H, et al.
  • Journal Title: Blood (in press)
• [Journal Article] Differential expression and function of Toll-like receptors in Langerhans cells : comparison with splenic dendritic cells. (2004)
  • Author(s): Mitsui H, Watanabe T, Saeki H, Mori K, Fujita H, et al.
  • Journal Title: J Invest Dermatol 122 Pages: 95-102
• [Journal Article] Differential effects of LPS and TGF-beta on the production of IL-6 and IL-12 by Langerhans cells, splenic dendritic cells, and macrophages. (2004)
  • Author(s): Tada Y, Asahina A, Fujita H, Mitsui H, Watanabe T, et al.
  • Journal Title: Cytokine 25 Pages: 155-161
• [Journal Article] Eccrine poroma associated with Bowen's disease. (2004)
  • Author(s): Watanabe T, Murakami T, Okochi H, Kikuchi K, Furue M.
  • Journal Title: Int J Dermatol 43 Pages: 472-473
• [Journal Article] Mucinous carcinoma of the skin could have either an eccrine or an apocrine origin. (2004)
  • Author(s): Mitsui H, Watanabe T, Jinnin M, Kadono T, Idezuki T, et al.
  • Journal Title: Br J Dermatol 151 Pages: 1285-1286
• [Journal Article] Focal palmoplantar callosities in non-Herlitz junctional epidermolysis bullosa. (2004)
  • Author(s): Mitsui H, Watanabe T, Komine M, Nakamura H, Shimizu H, et al.
  • Journal Title: J Am Acad Dermatol 52 Pages: 371-373
• [Publications] Watanabe T, Sugaya M, Atkins AM, Aquilino EA, Yang A, Borris DL, et al.: "Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen prolongs the life span of primary human umbilical vein endothelial cells."Journal of Virology. 77. 6188 (2003)
• [Publications] Mitsui H, Watanabe T, Saeki H, Mori K, Fujita H, Tada Y, et al.: "Differential expression and function of Toll-like receptors in Langerhans cells : comparison with splenic dendritic cells."Journal of Investigative Dermatology. (in press).
• [Publications] Tada Y, Asahina A, Fujita H, Mitsui H, Torii H, Watanabe T, et al.: "Differential effects of LPS and TGF-β on the production of IL-6 and IL-12 by Langerhans cells, splenic dendritic cells, and macrophages."Cytokine. (in press).