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T cell surveillance mechanisms in peripheral tissues

Research Project

Project/Area Number 19K08748
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53050:Dermatology-related
Research InstitutionKyoto University

Principal Investigator

EGAWA GYOHEI  京都大学, 医学研究科, 講師 (50511812)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
KeywordsT cell / homeostatic expansion / skin / homeostasis / T細胞 / 皮膚免疫 / 骨髄移植 / 抗原提示 / 樹状細胞 / ケモカイン / 生体イメージング
Outline of Research at the Start

エフェクターT細胞は、獲得免疫において中心的な役割を担う細胞群である。本細胞群は、血液中を循環し炎症部位へ集積するのみならず、炎症の生じていない末梢組織にも自ら浸潤し、非自己抗原の検索(homeostaticサーベイランス)を行うと考えられている。しかしその実態およびメカニズムについては不明の点が多い。本研究は、この「静の免疫応答」にスポットをあて、炎症のない状態の皮膚へのT細胞浸潤メカニズムの解明をめざす異色の研究である。Homeostaticサーベイランスが過剰に生じるマウスモデルを独自に考案し、遺伝子改変マウス、生体イメージングといったツールを駆使して本目的の達成を目指す。

Outline of Final Research Achievements

In this study, we aimed to elucidate how T cells infiltrate into non-inflamed skin using "homeostatic expansion" model. In this model, T cells proliferated markedly by 7 days after transfer, and many T cells migrated to the skin without inflammation. Almost all proliferated T cells were memory-phenotype (CD44+) and showed a tendency to differentiate into Th1 and Th17. In vivo imaging showed that CD8+ T cells infiltrated into the epidermis, especially around the hair follicles, and remained in the skin for more than 60 days. Dermatitis developed spontaneously when regulatory T cells are excluded during T cell transfer.

Academic Significance and Societal Importance of the Research Achievements

抗原非特異的にT細胞が増殖するHomeostatic expansionという現象は、生理的には新生児期、骨髄移植後、免疫抑制状態(AIDS患者や免疫抑制剤使用患者)からの回復時などで見られる。これらの状態では、新生児中毒性紅斑、脂漏性皮膚炎、好酸球性膿疱性毛包炎、免疫再構築症候群(IRIS)などの病態が生じることが知られる。本研究の成果からこれらの病態では炎症のない皮膚へのT細胞浸潤が増加し、host-parasite relationshipの変化が生じることが示唆された。この現象のメカニズム解明が進めば、これらの病態を制御する新たな治療標的などへとつながる可能性がある。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (38 results)

All 2023 2022 2021 2020 2019 2018

All Journal Article (25 results) (of which Int'l Joint Research: 10 results,  Peer Reviewed: 23 results,  Open Access: 9 results) Presentation (11 results) (of which Int'l Joint Research: 6 results,  Invited: 8 results) Book (2 results)

  • [Journal Article] Mast cells in type 2 skin inflammation: Maintenance and function2023

    • Author(s)
      Keith Yuki Honda、Egawa Gyohei、Honda Tetsuya、Kabashima Kenji
    • Journal Title

      European Journal of Immunology

      Volume: In press Issue: 8 Pages: 2250359-2250359

    • DOI

      10.1002/eji.202250359

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A case of Kimura disease with atopic dermatitis successfully treated with baricitinib2023

    • Author(s)
      Ueda Marina、Kogame Toshiaki、Egawa Gyohei、Kambe Naotomo、Kabashima Kenji
    • Journal Title

      The Journal of Dermatology

      Volume: In press Issue: 6 Pages: 196-197

    • DOI

      10.1111/1346-8138.16724

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Waves of layered immunity over innate lymphoid cells2022

    • Author(s)
      Kogame Toshiaki、Egawa Gyohei、Nomura Takashi、Kabashima Kenji
    • Journal Title

      Frontiers in Immunology

      Volume: 13

    • DOI

      10.3389/fimmu.2022.957711

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Phenotypic Analysis of Involucrin?Membrane-Bound Ovalbumin Mice after Adoptive Transfer of Ovalbumin-Specific CD8+ T Cells2022

    • Author(s)
      Nakagawa Yujin、Egawa Gyohei、Miyake Toshiya、Nakajima Saeko、Otsuka Atsushi、Nomura Takashi、Kitoh Akihiko、Dainichi Teruki、Sakabe Jun-ichi、Shibaki Akihiko、Tokura Yoshiki、Honda Tetsuya、Kabashima Kenji
    • Journal Title

      JID Innovations

      Volume: 2 Issue: 5 Pages: 100127-100127

    • DOI

      10.1016/j.xjidi.2022.100127

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Circadian rhythm affects the magnitude of contact hypersensitivity response in mice2022

    • Author(s)
      Miyake Toshiya、Egawa Gyohei、Chow Zachary、Asahina Ryota、Otsuka Masayuki、Nakajima Saeko、Nomura Takashi、Shibuya Rintaro、Ishida Yoshihiro、Nakamizo Satoshi、Murata Teruasa、Kitoh Akihiko、Kabashima Kenji
    • Journal Title

      Allergy

      Volume: 77 Issue: 9 Pages: 2748-2759

    • DOI

      10.1111/all.15314

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] CCL2?CCR2 Signaling in the Skin Drives Surfactant-Induced Irritant Contact Dermatitis through IL-1β?Mediated Neutrophil Accumulation2022

    • Author(s)
      Shibuya Rintaro、Ishida Yoshihiro、Hanakawa Sho、Kataoka Tatsuki R.、Takeuchi Yasuhide、Murata Teruasa、Akagi Arisa、Chow Zachary、Kogame Toshiaki、Nakamizo Satoshi、Nakajima Saeko、Egawa Gyohei、Nomura Takashi、Kambe Naotomo、Kitoh Akihiko、Kabashima Kenji
    • Journal Title

      Journal of Investigative Dermatology

      Volume: 142 Issue: 3 Pages: 571-582

    • DOI

      10.1016/j.jid.2021.07.182

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prolonged high-intensity exercise induces fluctuating immune responses to herpes simplex virus infection via glucocorticoids2021

    • Author(s)
      Adachi, A., Honda, T., Dainichi, T., Egawa, G., Yamamoto, Y., Nomura, T., Nakajima, S., Otsuka, A., Maekawa, M., Mano, N., Koyanagi, N., Kawaguchi, Y., Ohteki, T., Nagasawa, T., Ikuta, K., Kitoh, A., and Kabashima, K.
    • Journal Title

      J. Allergy Clin. Immunol.

      Volume: 148 Issue: 6 Pages: 1575-1588.e7

    • DOI

      10.1016/j.jaci.2021.04.028

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A new player in the dermis2021

    • Author(s)
      Egawa Gyohei、Kabashima Kenji
    • Journal Title

      eLife

      Volume: 10

    • DOI

      10.7554/elife.68979

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Putative Immunological Functions of Inducible Skin-Associated Lymphoid Tissue in the Context of Mucosa-Associated Lymphoid Tissue2021

    • Author(s)
      Kogame Toshiaki、Kabashima Kenji、Egawa Gyohei
    • Journal Title

      Frontiers in Immunology

      Volume: 12 Pages: 733484-733484

    • DOI

      10.3389/fimmu.2021.733484

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cutaneous Liver X Receptor Activation Prevents the Formation of Imiquimod-Induced Psoriatic Dermatitis.2021

    • Author(s)
      Otsuka M., Egawa G., Dainichi T., Okuno T., Ishida Y., Chow Z., Asahina R., Miyake T., Nomura T., Kitoh A., Yokomizo T., Kabashima K.
    • Journal Title

      Journal of Investigative Dermatology

      Volume: 142(4) Issue: 4 Pages: 1233-1237.e1

    • DOI

      10.1016/j.jid.2021.08.432

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PD-L1 on mast cells suppresses effector CD8+ T-cell activation in the skin in murine contact hypersensitivity2021

    • Author(s)
      Hirano Tomoko、Honda Tetsuya、Kanameishi Shuto、Honda Yuki、Egawa Gyohei、Kitoh Akihiko、Nakajima Saeko、Otsuka Atsushi、Nomura Takashi、Dainichi Teruki、Yaguchi Tomonori、Inozume Takashi、Kataoka Tatsuki R.、Tamada Koji、Kabashima Kenji
    • Journal Title

      Journal of Allergy and Clinical Immunology

      Volume: in press Issue: 2 Pages: 00178-00178

    • DOI

      10.1016/j.jaci.2020.12.654

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Intravital Imaging of Vascular Permeability by Two-Photon Microscopy.2021

    • Author(s)
      Egawa G, Ono S, Kabashima K.
    • Journal Title

      Methods Mol Biol.

      Volume: 2223 Pages: 151-157

    • DOI

      10.1007/978-1-0716-1001-5_11

    • ISBN
      9781071610008, 9781071610015
    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Bacterial antigen is directly delivered to the draining lymph nodes and activates CD8+ T cells during Staphylococcus aureus skin infection.2020

    • Author(s)
      Egawa G, Roediger B, Tay SS, L Cavanagh L, V Guy T, Fazekas de B, Brzoska AJ, Firth N, Weninger W.
    • Journal Title

      Immunol Cell Biol. 2021 Mar;99(3):299-308

      Volume: 99 Issue: 3 Pages: 299-308

    • DOI

      10.1111/imcb.12410

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] THE MECHANISM OF ITCH2020

    • Author(s)
      江川形平
    • Journal Title

      Japanese Journal of Allergology

      Volume: 69 Issue: 4 Pages: 256-259

    • DOI

      10.15036/arerugi.69.256

    • NAID

      130007853937

    • ISSN
      0021-4884, 1347-7935
    • Related Report
      2020 Research-status Report
  • [Journal Article] Role of Lymphoid Structure in Skin Immunity.2020

    • Author(s)
      Egawa G, Kabashima K.
    • Journal Title

      Curr Top Microbiol Immunol.

      Volume: 426 Pages: 65-82

    • DOI

      10.1007/82_2020_206

    • ISBN
      9783030517465, 9783030517472
    • Related Report
      2020 Research-status Report
  • [Journal Article] IN VIVO IMAGING OF CUTANEOUS INFLAMMATION: NOVEL INSIGHTS INTO CUTANEOUS IMMUNE RESPONSES REVEALED BY INTRAVITAL IMAGING TECHNIQUES2020

    • 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
    • Related Report
      2019 Research-status Report
    • 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

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Abl family tyrosine kinases govern IgG extravasation in the skin in a murine pemphigus model2019

    • 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

    • Related Report
      2019 Research-status Report
    • 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

    • Related Report
      2019 Research-status Report
    • 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

    • Related Report
      2019 Research-status Report
    • 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

    • Related Report
      2019 Research-status Report
    • 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

    • Related Report
      2019 Research-status Report
    • 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

    • Related Report
      2019 Research-status Report
    • 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

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Intravital imaging of cutaneous immune responses2018

    • 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

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Expanded T cells under lymphopenic condition exhibits memory phenotype and infiltrate around hair follicle2023

    • Author(s)
      石橋茉実、江川形平、椛島健治
    • Organizer
      International Societies for Investigative Dermatology
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The role of IL-23 in the pathogenesis of psoriasis : update your knowledge2021

    • Author(s)
      江川形平
    • Organizer
      第50回日本免疫学会学術大会
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Revisiting the dogma of contact dermatitis; even single hapten application can induce allergic contact dermatitis in situ2021

    • Author(s)
      江川形平
    • Organizer
      第46回日本研究皮膚科学会
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Itching mechanism in Atopic Dermatitis -from basic to clinical2021

    • Author(s)
      江川形平
    • Organizer
      第46回日本研究皮膚科学会
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 乾癬病態の基礎的知見: 最近のトピックス2021

    • Author(s)
      江川形平
    • Organizer
      第51回日本皮膚免疫アレルギー学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 末梢組織リンパ管を場とした免疫制御機構の解明2021

    • Author(s)
      江川形平
    • Organizer
      第120回日本皮膚科学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 皮膚免疫細胞の可視化2021

    • Author(s)
      江川形平
    • Organizer
      第120回日本皮膚科学会総会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Two-photon microscopy_ its application to skin research2019

    • Author(s)
      江川形平
    • Organizer
      World Congress of Dermatology
    • Related Report
      2019 Research-status Report
    • 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
    • Related Report
      2019 Research-status Report
    • 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
    • Related Report
      2019 Research-status Report
    • 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
    • Related Report
      2019 Research-status Report
    • Invited
  • [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
    • Related Report
      2019 Research-status Report
  • [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
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2024-01-30  

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