T cell surveillance mechanisms in peripheral tissues
Project/Area Number |
19K08748
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 53050:Dermatology-related
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Research Institution | Kyoto University |
Principal Investigator |
EGAWA GYOHEI 京都大学, 医学研究科, 講師 (50511812)
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Project Period (FY) |
2019-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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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)
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Keywords | T 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。
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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.
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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。
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Report
(5 results)
Research Products
(38 results)
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[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.
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Journal Title
J. Allergy Clin. Immunol.
Volume: 148
Issue: 6
Pages: 1575-1588.e7
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
Journal of Investigative Dermatology
Volume: 142(4)
Issue: 4
Pages: 1233-1237.e1
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
J Dermatol Sci
Volume: -
Issue: 2
Pages: 0-0
DOI
Related Report
Peer Reviewed
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[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.
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Journal Title
Nat Commun
Volume: 10(1)
Issue: 1
Pages: 4432-4432
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[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
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Journal Title
Trials
Volume: 20(1)
Issue: 1
Pages: 489-489
DOI
NAID
Related Report
Peer Reviewed
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[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.
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Journal Title
J Allergy Clin Immunol
Volume: 144(4)
Issue: 4
Pages: 1036-1049
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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.
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Journal Title
J Allergy Clin Immunol
Volume: 144(5)
Issue: 5
Pages: 1265-1273
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
J Allergy Clin Immunol. 2019
Volume: 144(5)
Issue: 5
Pages: 1343-1353
DOI
Related Report
Peer Reviewed
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[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.
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Journal Title
J Allergy Clin Immunol. 2019
Volume: 144(2)
Issue: 2
Pages: 617-620
DOI
Related Report
Peer Reviewed
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