皮膚免疫と全身免疫のクロストークの可能性の検証とその役割

• Project/Area Number: 12J02006
• Research Category: Grant-in-Aid for JSPS Fellows
• Allocation Type: Single-year Grants
• Section: 国内
• Research Field: 皮膚科学
• Research Institution: Kyoto University
• Principal Investigator: 中溝 聡 京都大学, 医学研究科, 特別研究員(DC1)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥2,700,000 (Direct Cost: ¥2,700,000); Fiscal Year 2014: ¥900,000 (Direct Cost: ¥900,000); Fiscal Year 2013: ¥900,000 (Direct Cost: ¥900,000); Fiscal Year 2012: ¥900,000 (Direct Cost: ¥900,000)
• Keywords: gdT cell / 皮膚感染症 / 皮膚 / T細胞 / 樹状細胞

Outline of Annual Research Achievements

皮膚gdT細胞の組織間循環動態と獲得免疫における役割
■背景と問題点　gd T細胞は細菌感染時における皮膚局所の自然免疫応答に重要な細胞である。一方、獲得免疫の場であるリンパ節にもgdT細胞は存在する(Sumaria et al. J Exp Med. 2011)。しかしながら、皮膚gd T細胞とリンパ節gdT細胞の循環動態とその関係性、及び皮膚gdT細胞の獲得免疫に対する作用はほとんどわかっていなかった。
■研究方法　カエデマウス(紫外線照射により生体において細胞を蛍光ラベルできる)の皮膚にBCGを感染させ、皮膚gdT細胞のリンパ節への循環動態を解析した。また循環gdT細胞のリンパ節における機能解析を行った。
■研究経過及び得られた結果　皮膚に抗原が侵入するとgdT細胞は皮膚からリンパ節へ移動し、樹状細胞を活性化することで、間接的にT細胞分化を調整することが明らかになった。これは皮膚炎の局所治療により全身性の感作も制御できる可能性を示唆している。

Research Progress Status

26年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

26年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Dermal Vγ4(+) γδ T Cells Possess a Migratory Potency to the Draining Lymph Nodes and Modulate CD8(+) T-Cell Activity through TNF-α Production. (2015)
  • Author(s): Nakamizo S, Egawa G, Tomura M, Sakai S, Tsuchiya S, Kitoh A, Honda T, Otsuka A, Nakajima S, Dainichi T, Tanizaki H, Mitsuyama M, Sugimoto Y, Kawai K, Yoshikai Y, Miyachi Y, Kabashima K.
  • Journal Title: Journal of Investigative Dermatology Volume: 135 Issue: 4 Pages: 1007-1015
  • DOI: 10.1038/jid.2014.516
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Commensal bacteria and cutaneous immunity. (2015)
  • Author(s): Nakamizo S, Egawa G, Honda T, Nakajima S, Belkaid Y, Kabashima K.
  • Journal Title: Seminars in Immunopathology Volume: 37 Issue: 1 Pages: 73-80
  • DOI: 10.1007/s00281-014-0452-6
  • Peer Reviewed
• [Journal Article] Possible new therapeutic strategy to regulate atopic dermatitis through upregulating filaggrin expression. (2014)
  • Author(s): Otsuka A, Doi H, Egawa G, Maekawa A. Fujita T, Nakamizo S, et al.
  • Journal Title: J Allergy Clin Immunol. Volume: 133(1) Issue: 1 Pages: 139-46
  • DOI: 10.1016/j.jaci.2013.07.027
  • Peer Reviewed
• [Journal Article] Acquired generalised anhidrosis presenting with heat retention after carboplatin and pachtaxel treatment. (2013)
  • Author(s): Endo Y, Nakamizo S, Fujisawa A, Tanioka M, Kabashima K, Miyaehi Y
  • Journal Title: Eur J Dermatrol. Volume: 23(6) Issue: 6 Pages: 139-46
  • DOI: 10.1684/ejd.2013.2202
  • Peer Reviewed
• [Journal Article] A double dose of levocetirizine leads to better control of histamine-induced flare, wheal and itch in healthy donors. (2013)
  • Author(s): Tanizaki H, Nakamizo S, et al.
  • Journal Title: Pharmacology. Volume: 92(1-2) Issue: 1-2 Pages: 71-4
  • DOI: 10.1159/000353191
  • Peer Reviewed
• [Journal Article] Intravital analysis of vascular permeability in mice using two-photon microscopy. (2013)
  • Author(s): Egawa G, Nakamizo S., et al.
  • Journal Title: Sci Rep. Volume: 3 Issue: 1 Pages: 1932-1932
  • DOI: 10.1038/srep01932
  • Peer Reviewed
• [Journal Article] Mast cell maturation is driven via a novel group III phospholipase A2-prostaglandin D2-DP1 receptor paracrine axis. (2013)
  • Author(s): Taketomi, Y., Morimoto, K., Murakami, M., et al., 他30名
  • Journal Title: Nature Immunol. Volume: (印刷中) Issue: 6 Pages: 554-63
  • DOI: 10.1038/ni.2586
  • Peer Reviewed
• [Journal Article] Atypical nail dystrophy in a possible case of Nagashima-type palmoplanar keratosis. (2012)
  • Author(s): Nakamizo S, Katoh N, Miyachi Y, Kabashima K.
  • Journal Title: J Dermatol Volume: 39 Issue: 5 Pages: 470-1
  • DOI: 10.1111/j.1346-8138.2011.01326.x
  • Peer Reviewed
• [Journal Article] Simultaneous occurrence of distantly located multiple sebaceous carcinomas with elevated serum TGF-ss in Muir-Torre syndrome. (2012)
  • Author(s): Nakamizo S, Arakawa A, Kitoti A, Kore-Eda S, Utani A, Miyachi Y.
  • Journal Title: Eur J Dermatol. Volume: 22 Issue: 3 Pages: 417-8
  • DOI: 10.1684/ejd.2012.1705
  • Peer Reviewed
• [Journal Article] Topical Treatment with Basic Fibroblast Growth Factor Promotes Wound Healing and Barrier Recovery Induced by Skin Abrasion. (2012)
  • Author(s): Nakamizo S, Egawa G, Doi H, Natsuaki Y, Miyachi Y, Kabashima K.
  • Journal Title: Skin Pharmacol Physiol. Volume: 26 Pages: 22-29
  • Peer Reviewed
• [Presentation] High fat diet contributes to cutaneous IL-17 producing gamma delta T cell recruitment and exacerbates imiquimod-induced psoriatic dermatitis (2014)
  • Author(s): 中溝 聡
  • Organizer: 日本研究皮膚科学会 第39回年次学術大会・総会
  • Place of Presentation: ホテル阪急エキスポパーク
  • Year and Date: 2014-12-12 – 2014-12-14
• [Presentation] High fat diet exacerbates imiquimod-induced psoriatic dermatitis via increasing IL-17-producing dermal gamma delta T cells (2014)
  • Author(s): 中溝 聡
  • Organizer: 第43回日本免疫学会学術集会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Newly identification of a migration subset of dermal γδ T cells that initiate contact hypersensitivity by producing TNF-alpha in the lymph nodes (2013)
  • Author(s): 中溝聡、江川形平、宮地良樹、椛島健治
  • Organizer: 国際研究皮膚科学会
  • Place of Presentation: エジンバラ(イギリス)