Immune cell-immune cell interactions in the peripheral lymph ducts

• Project/Area Number: 17K19655
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: General internal medicine and related fields
• Research Institution: Kyoto University
• Principal Investigator: Egawa Gyohei 京都大学, 医学研究科, 助教 (50511812)
• Project Period (FY): 2017-06-30 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2018: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2017: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: リンパ管 / T細胞 / 樹状細胞 / 接触過敏反応 / 接触皮膚炎 / イメージング / 免疫学 / 皮膚免疫

Outline of Final Research Achievements

It is generally considered that lymph ducts are a “tube” which connecting peripheral tissue and lymph nodes. Here we examined whether lymph ducts have any role during the development of skin inflammation. Without using transgenic animals, we established the techniques to visualize the lymph ducts in vivo, in an easy way. Using this technique, we observed the behavior of T cells and dendritic cells in the skin under the steady state and under the inflammatory states. We found that T cells and dendritic cells formed clusters in the lymph ducts during the development of skin inflammation. This observation suggests that the lymph ducts are not merely a tube, but they provide the sites for the T cell-dendritic cell interaction for the antigen presentation.

Academic Significance and Societal Importance of the Research Achievements

本研究はこれまで免疫学的には細胞間質液（リンパ液）やリンパ節へ移動する免疫細胞の通り道としてしか認識されていなかったリンパ管が、皮内におけるT細胞と樹状細胞の会合、すなわち抗原提示の場を提供している可能性を明らかにした。末梢組織における抗原提示は炎症の惹起において中心となる免疫事象であり、皮膚においては血管周囲や毛包の周囲で行われている可能性が報告されているものの、リンパ管との関連を示唆する報告はこれまでにない。今後の研究でリンパ管内における抗原提示の分子メカニズムが明らかとなりそれを特異的に阻害することが可能となれば、免疫疾患の新たな治療ストラテジーとなる可能性がある。

Research Products

• [Journal Article] IN VIVO IMAGING OF CUTANEOUS INFLAMMATION: NOVEL INSIGHTS INTO CUTANEOUS IMMUNE RESPONSES REVEALED BY INTRAVITAL IMAGING TECHNIQUES (2020)
  • Author(s): Honda T, Egawa G, Kabashima K.
  • Journal Title: Japanese Journal of Allergology Volume: 69 Issue: 2 Pages: 93-98
  • DOI: 10.15036/arerugi.69.93
  • NAID: 130007809360
  • ISSN: 0021-4884, 1347-7935
  • Peer Reviewed
• [Journal Article] Janus kinase inhibitor delgocitinib suppresses pruritus and nerve elongation in an atopic dermatitis murine model. (2020)
  • Author(s): Yamamoto Y, Otsuka A, Nakashima C, Ishida Y, Honda T, Egawa G, Amano W, Usui K, Hamada Y, Wada M, Tanimoto A, Konishi N, Hayashi M, Matsushita M, Kabashima K.
  • Journal Title: J Dermatol Sci Volume: － Issue: 2 Pages: 0-0
  • DOI: 10.1016/j.jdermsci.2019.12.008
  • Peer Reviewed
• [Journal Article] Abl family tyrosine kinases govern IgG extravasation in the skin in a murine pemphigus model (2019)
  • Author(s): Ono S, Egawa G, Nomura T, Kitoh A, Dainichi T, Otsuka A, Nakajima S, Amagai M, Matsumoto F, Yamamoto M, Kubota Y, Takai T, Honda T, Kabashima K.
  • Journal Title: Nat Commun Volume: 10(1) Issue: 1 Pages: 4432-4432
  • DOI: 10.1038/s41467-019-12232-3
  • NAID: 120006731596
  • Peer Reviewed / Open Access
• [Journal Article] The efficacy of a cyclin dependent kinase 9 (CDK9)inhibitor, FIT039, on verruca vulgaris: study protocol for a randomized controlled trial. (2019)
  • Author(s): Nomura T, Sumi E, Egawa G, Nakajima S, Toichi E, Uozumi R, Tada H, Nakagawa T, Hagiwara M, Kabashima K
  • Journal Title: Trials Volume: 20(1) Issue: 1 Pages: 489-489
  • DOI: 10.1186/s13063-019-3570-6
  • NAID: 120006796395
  • Peer Reviewed
• [Journal Article] Cutaneous p38 mitogen-activated protein kinase activation triggers psoriatic dermatitis. (2019)
  • Author(s): Sakurai K, Dainichi T, Garcet S, Tsuchiya S, Yamamoto Y, Kitoh A, Honda T, Nomura T, Egawa G, Otsuka A, Nakajima S, Matsumoto R, Nakano Y, Otsuka M, Iwakura Y, Grinberg-Bleyer Y, Ghosh S, Sugimoto Y, Guttman-Yassky E, Krueger JG, Kabashima K.
  • Journal Title: J Allergy Clin Immunol Volume: 144(4) Issue: 4 Pages: 1036-1049
  • DOI: 10.1016/j.jaci.2019.06.019
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prostaglandin E(2) (PGE(2))-EP2signaling negatively regulates murine atopic dermatitis-like skin inflammation by suppressing thymic stromal lymphopoietin expression. (2019)
  • Author(s): Sawada Y, Honda T, Nakamizo S, Nakajima S, Nonomura Y, Otsuka A, Egawa G, Yoshimoto T, Nakamura M, Narumiya S, Kabashima K.
  • Journal Title: J Allergy Clin Immunol Volume: 144(5) Issue: 5 Pages: 1265-1273
  • DOI: 10.1016/j.jaci.2019.06.036
  • Peer Reviewed / Open Access
• [Journal Article] Percutaneous sensitization is limited by in situ inhibition of cutaneous dendritic cell migration through skin-resident regulatory T cells. (2019)
  • Author(s): Hanakawa S, Kitoh A, Shibuya R, Dainichi T, Nomura T, Honda T, Egawa G, Otsuka A, Nakajima S, Fujita M, Kabashima K.
  • Journal Title: J Allergy Clin Immunol. 2019 Volume: 144(5) Issue: 5 Pages: 1343-1353
  • DOI: 10.1016/j.jaci.2019.05.033
  • Peer Reviewed
• [Journal Article] Murine neonatal skin mast cells are phenotypically immature and minimally sensitized with transplacentally transferred IgE. (2019)
  • Author(s): Honda Y, Ono S, Honda T, Kataoka TR, Egawa G, Kitoh A, Otsuka A, Nakajima S, Nomura T, Dainichi T, Kabashima K.
  • Journal Title: J Allergy Clin Immunol. 2019 Volume: 144(2) Issue: 2 Pages: 617-620
  • DOI: 10.1016/j.jaci.2019.05.011
  • Peer Reviewed
• [Journal Article] Antigen presentation and adaptive immune responses in skin. (2019)
  • Author(s): Honda T, Egawa G, Kabashima K.
  • Journal Title: Int Immunol. Volume: 0 Issue: 7 Pages: 0-0
  • DOI: 10.1093/intimm/dxz005
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Long-term efficacy of ixekizumab in erythrodermic and generalized pustular psoriasis patients (2019)
  • Author(s): Egawa G.、Honda T.、Kabashima K.
  • Journal Title: Journal of the European Academy of Dermatology and Venereology Volume: 33 Issue: 2 Pages: 259-259
  • DOI: 10.1111/jdv.15416
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Pathomechanism of ‘skin-originated’ allergic diseases (2018)
  • Author(s): Egawa Gyohei
  • Journal Title: Immunological Medicine Volume: 41 Issue: 4 Pages: 170-176
  • DOI: 10.1080/25785826.2018.1540257
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Live Imaging of the Skin Immune Responses: Visualization of the Contact Hypersensitivity Response (2018)
  • Author(s): Egawa Gyohei、Honda Tetsuya、Kabashima Kenji
  • Journal Title: Dendritic Cell Protocols Volume: 3 Pages: 75-85
  • DOI: 10.1007/978-1-4939-7762-8_8
  • ISBN: 9781493977611, 9781493977628
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Barrier dysfunction in the skin allergy (2018)
  • Author(s): Egawa Gyohei、Kabashima Kenji
  • Journal Title: Allergology International Volume: 67 Issue: 1 Pages: 3-11
  • DOI: 10.1016/j.alit.2017.10.002
  • NAID: 130006322087
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The immunological anatomy of the skin (2018)
  • Author(s): Kabashima Kenji、Honda Tetsuya、Ginhoux Florent、Egawa Gyohei
  • Journal Title: Nature Reviews Immunology Volume: 19 Issue: 1 Pages: 19-30
  • DOI: 10.1038/s41577-018-0084-5
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Intravital imaging of cutaneous immune responses (2018)
  • Author(s): Nakamizo Satoshi、Egawa Gyohei、Tan Kahbing Jasmine、Kabashima Kenji
  • Journal Title: Cellular Immunology Volume: - Pages: 103813-103813
  • DOI: 10.1016/j.cellimm.2018.05.006
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Intravenous immunoglobulin treatment abrogates transplacental autoantibody transfer in a murine pemphigus model (2018)
  • Author(s): Sachiko Ono, Gyohei Egawa, Tetsuya Honda, and Kenji Kabashima
  • Journal Title: Journal of Allergy and Clinical Immunology Volume: 印刷中 Issue: 6 Pages: 2273-2276.e1
  • DOI: 10.1016/j.jaci.2017.12.985
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Uncovering the Mysteries of Langerhans Cells, Inflammatory Dendritic Epidermal Cells, and Monocyte-Derived Langerhans Cell-Like Cells in the Epidermis (2018)
  • Author(s): Otsuka Masayuki、Egawa Gyohei、Kabashima Kenji
  • Journal Title: Frontiers in Immunology Volume: 9
  • DOI: 10.3389/fimmu.2018.01768
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A case of atypical eosinophilic pustular folliculitis that emerged following the administration of capecitabine (2018)
  • Author(s): Takeuchi A.、Nomura T.、Kaku Y.、Egawa G.、Kabashima K.
  • Journal Title: Journal of the European Academy of Dermatology and Venereology Volume: 32 Issue: 8
  • DOI: 10.1111/jdv.14871
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Thromboxane A2 facilitates IL-17A production from Vγ4+ γδ T cells and promotes psoriatic dermatitis in mice. (2018)
  • Author(s): Ueharaguchi Y, Honda T, Kusuba N, Hanakawa S, Adachi A, Sawada Y, Otsuka A, Kitoh A, Dainich T, Egawa G, Nakachima C, Nakajima S, Murata T, Ono S, Arita M, Narumiya S, Miyachi Y, Kabashima K
  • Journal Title: Journal of Allergy and Clinical Immunology Volume: in press Issue: 2 Pages: 680-683.e2
  • DOI: 10.1016/j.jaci.2018.01.054
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Negative Evidence of Direct Differentiation from Bone-Marrow Cells to Keratinocytes in Normal and Wounded Skin Using Keratin 5-Specific Reporter Mice (2018)
  • Author(s): Egawa Gyohei、Kabashima Kenji
  • Journal Title: Journal of Investigative Dermatology Volume: 138 Issue: 5 Pages: 1228-1231
  • DOI: 10.1016/j.jid.2017.12.032
  • Peer Reviewed
• [Journal Article] Inhibition of IL-17 committed T cells in a murine psoriasis model by a vitamin D analogue (2018)
  • Author(s): Kusuba Nobuhiro、Kitoh Akihiko、Dainichi Teruki、Honda Tetsuya、Otsuka Atsushi、Egawa Gyohei、Nakajima Saeko、Miyachi Yoshiki、Kabashima Kenji
  • Journal Title: J Allergy Clin Immunol. Volume: 141 Issue: 3 Pages: 972-981.e10
  • DOI: 10.1016/j.jaci.2017.07.033
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Regulation of blood vascular permeability in the skin (2017)
  • Author(s): Ono Sachiko、Egawa Gyohei、Kabashima Kenji
  • Journal Title: Inflammation and Regeneration Volume: 37 Issue: 1 Pages: 11-15
  • DOI: 10.1186/s41232-017-0042-9
  • Peer Reviewed / Open Access
• [Journal Article] High fat diet exacerbates murine psoriatic dermatitis by increasing the number of IL-17-producing γδ T cells (2017)
  • Author(s): Nakamizo Satoshi、Honda Tetsuya、Adachi Akimasa、Nagatake Takahiro、Kunisawa Jun、Kitoh Akihiko、Otsuka Atsushi、Dainichi Teruki、Nomura Takashi、Ginhoux Florent、Ikuta Koichi、Egawa Gyohei、Kabashima Kenji
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 999-999
  • DOI: 10.1038/s41598-017-14292-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] RIPK3 controls keratinocyte activation in a necroptosis-independent manner and promotes psoriatic dermatitis in mice (2017)
  • Author(s): Tetsuya Honda, Osamu Yamamoto MD, Yu Sawada, Gyohei Egawa, Akihiko Kitoh, Atsushi Otsuka, Teruki Dainichi, Saeko Nakajima, Yoshiki Miyachi, Kenji Kabashima
  • Journal Title: Journal of Allergy and Clinical Immunology Volume: 5 Issue: 2 Pages: 619-622.e6
  • DOI: 10.1016/j.jaci.2017.02.027
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] SCFAs Control Skin Immune Responses via Increasing Tregs (2017)
  • Author(s): Egawa Gyohei、Honda Tetsuya、Kabashima Kenji
  • Journal Title: J Invest Dermatol. Volume: 137 Issue: 4 Pages: 800-801
  • DOI: 10.1016/j.jid.2016.12.022
  • Peer Reviewed
• [Journal Article] Local inflammation exacerbates cutaneous manifestations in a murine autoimmune pemphigus model (2017)
  • Author(s): S. Ono, G. Egawa, A. Kitoh, T. Dainichi, A. Otsuka, S. Nakajima, T, Honda, K. Kabashima
  • Journal Title: Journal of Allergy and Clinical Immunology Volume: 印刷中 Issue: 6 Pages: 2026-2028.e5
  • DOI: 10.1016/j.jaci.2016.12.959
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Two-photon microscopy_ its application to skin research (2019)
  • Author(s): 江川形平
  • Organizer: World Congress of Dermatology
  • Int'l Joint Research / Invited
• [Presentation] What skin barrier defect in atopic dermatitis teach us about epidermal physiology. (2019)
  • Author(s): 江川形平
  • Organizer: 日本研究皮膚科学会
  • Int'l Joint Research / Invited
• [Presentation] 皮膚のかゆみのメカニズム (2019)
  • Author(s): 江川形平
  • Organizer: 日本アレルギー学会学術大会
  • Invited
• [Presentation] 皮膚の防御における多段階的なT細胞の役割 (2019)
  • Author(s): 江川形平
  • Organizer: 日本臨床免疫学会
  • Invited
• [Presentation] 皮膚のバリアとアレルギー (2019)
  • Author(s): 江川形平
  • Organizer: 宮城県皮膚科地方会
  • Invited
• [Presentation] Intravital imaging of skin immune responses (2018)
  • Author(s): 江川形平
  • Organizer: 第45回皮膚科たち研究会
  • Int'l Joint Research / Invited
• [Presentation] 皮膚の免疫ステルスとイメージング (2018)
  • Author(s): 江川形平
  • Organizer: 第91回日本生化学会総会
  • Int'l Joint Research / Invited
• [Presentation] 皮膚のバリアとアレルギー (2018)
  • Author(s): 江川形平
  • Organizer: 第46回日本臨床免疫学会総会
  • Int'l Joint Research / Invited
• [Presentation] Lymph duct and cutaneous immune responses (2018)
  • Author(s): 江川形平
  • Organizer: 血栓止血学会総会
  • Invited
• [Presentation] リンパ管と皮膚免疫 (2018)
  • Author(s): 江川形平
  • Organizer: 日本血栓止血学会
  • Invited
• [Presentation] 皮膚免疫応答のライブイメージング (2017)
  • Author(s): 江川形平
  • Organizer: 第4回先進イメージング研究会
• [Presentation] T細胞からみた免疫記憶 (2017)
  • Author(s): 江川形平
  • Organizer: 六甲医学研究会
• [Presentation] In-vivo analysis of bacterial antigen delivery dynamics and T cell immunity against Staphylococcus aureus skin infection (2017)
  • Author(s): 江川形平
  • Organizer: Europian society for dermatological research (ESDR)
  • Int'l Joint Research
• [Presentation] Revisiting the concept of CHS response; effector T cells infiltrates into the hapten-entry sites and confer long-lasting local memory (2017)
  • Author(s): 江川形平
  • Organizer: 日本免疫学会
  • Int'l Joint Research
• [Book] Live Imaging of the Skin Immune Responses. (2020)
  • Author(s): Chow Z., Egawa G., Kabashima K.
  • Total Pages: 200
  • Publisher: Springer, Singapore
  • ISBN: 9789811379086
• [Book] 最新キーワードで読み解くALL About 皮膚科学＿ライブイメージング/二光子顕微鏡 (2019)
  • Author(s): 江川形平
  • Total Pages: 228
  • Publisher: メディカルレビュー社
  • ISBN: 9784779222351