Regulation of allergic and autoimmune responses by ILC2-T cell interaction
Project/Area Number |
20K08766
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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 54020:Connective tissue disease and allergy-related
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Research Institution | Tohoku University |
Principal Investigator |
Ishii Naoto 東北大学, 医学系研究科, 教授 (60291267)
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Co-Investigator(Kenkyū-buntansha) |
宗 孝紀 富山大学, 学術研究部薬学・和漢系, 教授 (60294964)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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Keywords | 2型自然リンパ球 / 腫瘍免疫 / アトピー性皮膚炎 / アレルギー / 自然リンパ球 / T細胞共刺激分子 / T細胞 |
Outline of Research at the Start |
本研究では、活性化した2型自然リンパ球表面に発現するGITR-LとOX40-LがT細胞の分化制御や活性化制御に直接的に関与することを証明する。ILC2上のこれらの分子がT細胞免疫寛容制御機構とT細胞分化制御に関与することを明らかにすることにより、アレルギー・膠原病発症の新たな制御機構を解明し、さらには、新たな治療法の開発に資する基盤技術の確立を目指す。
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Outline of Final Research Achievements |
We found that OX40-L is expressed on IL-33-stimulated group 2 innate lymphoid cells (ILC2) in mice and may exert anti-tumor effects by providing OX40 stimulation to killer T cells, an important finding indicating an immune activation mechanism through the interaction between ILC2 and T cells. We also found that OX40 expression on peripheral blood ILC2 of adult patients with atopic dermatitis was higher than that of healthy subjects. Furthermore, we found that the expression level of OX40 is positively correlated with the POEM score, an index of the severity of atopic dermatitis. The increased proliferation and expression of Th2 cytokines in in vitro OX40-stimulated ILC2 suggests that OX40-expressing ILC2 may be involved in the pathogenesis of atopic dermatitis.
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Academic Significance and Societal Importance of the Research Achievements |
OX40はT細胞に活性化シグナルを伝達する共刺激分子として知られており、人為的なOX40阻害はアレルギー・自己免疫疾患の治療標的であり、OX40刺激はヒトにおいても抗腫瘍効果を発揮する。OX40-OX40L系がILC2の活性化やT細胞との相互作用で機能するとの本知見は学術的にも臨床医学的にも重要な発見である。
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Report
(4 results)
Research Products
(19 results)
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[Journal Article] Redefining the Foreign Antigen and Self-Driven Memory CD4+ T-Cell Compartments via Transcriptomic, Phenotypic, and Functional Analyses2022
Author(s)
Kawabe T, Ciucci T, Kim KS, Tayama S, Kawajiri A, Suzuki T, Tanaka R, Ishii N, Jankovic D, Zhu J, Sprent J, Bosselut R, Sher A
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Journal Title
Front Immunol
Volume: 13
Pages: 870542-870542
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Phenotypic heterogeneity in individuals with MECOM variants in 2 families.2022
Author(s)
Niihori T, Tanoshima R, Sasahara Y, Sato A, Irie M, Saito-Nanjo Y, Funayama R, Shirota M, Abe T, Okuyama Y, Ishii N, Nakayama K, Kure S, Imaizumi M, Aoki Y.
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Journal Title
Blood Adv.
Volume: -
Issue: 18
Pages: 5257-5261
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] TNF Receptor-Associated Factor 5 Limits IL-27 Receptor Signaling in CD4 + T Lymphocytes2022
Author(s)
Kawahara E, Azuma M, Nagashima H, Omori K, Akiyama S, Fujimori Y, Oishi M, Shibui N, Kawaguchi K, Morita M, Okuyama Y, Ishii N, So T.
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Journal Title
J Immunol.
Volume: 208(3)
Issue: 3
Pages: 642-650
DOI
Related Report
Peer Reviewed
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[Journal Article] Phenotypic heterogeneity in individuals with MECOM variants in 2 families.2022
Author(s)
Niihori T, Tanoshima R, Sasahara Y, Sato A, Irie M, Saito-Nanjo Y, Funayama R, Shirota M, Abe T, Okuyama Y, Ishii N, Nakayama K, Kure S, Imaizumi M, Aoki Y
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Journal Title
Blood Adv
Volume: in press
Related Report
Peer Reviewed
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[Journal Article] The Curcumin Analog GO-Y030 Controls the Generation and Stability of Regulatory T Cells2021
Author(s)
Takashi MaruYama, Shuhei Kobayashi, Hiroko Nakatsukasa, Yuki Moritoki, Daiki Taguchi, Yoichi Sunagawa, Tatsuya Morimoto, Atsuko Asao, Wenwen Jin, Yuji Owada, Naoto Ishii, Yoshiharu Iwabuchi, Akihiko Yoshimura, WanJun Chen, Hiroyuki Shibata
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Journal Title
Frontiers in immunology
Volume: 12
Pages: 687669-687669
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Dysregulation of Rnf 213 gene contributes to T cell response via antigen uptake, processing, and presentation2021
Author(s)
Tashiro R, Niizuma K, Kasamatsu J, Okuyama Y, Rashad S, Kikuchi A, Fujimura M, Kure S, Ishii N, Tominaga T.
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Journal Title
J Cell Physiol.
Volume: 236(11)
Issue: 11
Pages: 7554-7564
DOI
Related Report
Peer Reviewed
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[Journal Article] Germ-free conditions modulate host purine metabolism, exacerbating adenine-induced kidney damage.2020
Author(s)
Mishima E, Ishijo M, Kawabe T, Kikuchi K, Akiyama Y, Toyohara T, Suzuki C, Asao A, Ishii N, Fukuda S, Abe T
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Journal Title
Toxins
Volume: 12
Issue: 9
Pages: 547-547
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] GITR controls intestinal inflammation by suppressing IL-15-dependent NK cell activity.2020
Author(s)
Sakurai T, Okuyama Y, Kobayashi S, Phung HT, Asao A, Kawabe T, Ndhlovu LC, Riccardi C, Kudo H, Wada M, Nio M, So T, Ishii N.
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Journal Title
FASEB J.
Volume: 34(11)
Issue: 11
Pages: 14820-14831
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Requirements for the differentiation of innate T-bethigh memory-phenotype CD4+ T lymphocytes under steady state.2020
Author(s)
Kawabe T, Yi J, Kawajiri A, Hilligan K, Fang D, Ishii N, Yamane H, Zhu J, Jankovic D, Kim KS, Trinchieri G, Sher A
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Journal Title
Nat Commun
Volume: 11
Issue: 1
Pages: 3366-3366
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Costello syndrome model mice with a HRAS G12S/+ mutation are susceptible to develop house dust mite-induced atopic dermatitis.2020
Author(s)
Katata Y, Inoue S-I, Asao A, Kobayashi S, Terui H, Inoue-Shibui A, Abe T, Niihori T, Aiba S, Ishii N, Kure S, Aoki Y
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Journal Title
Cell Death & Disease
Volume: 11
Issue: 8
Pages: 617-617
DOI
Related Report
Peer Reviewed / Open Access