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Identification and analysis of the niches for helper memory T cells

Research Project

Project/Area Number 15H04742
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionTohoku University

Principal Investigator

ISHII Naoto  東北大学, 医学系研究科, 教授 (60291267)

Co-Investigator(Kenkyū-buntansha) 宗 孝紀  東北大学, 医学系研究科, 准教授 (60294964)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2016: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2015: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Keywords記憶T細胞 / ニッチ / 腸管膜リンパ節 / Th17細胞 / 炎症 / 免疫記憶 / ヘルパーT細胞 / リンパ節 / 自己免疫疾患 / 免疫学 / アレルギー / T細胞 / 腸管免疫
Outline of Final Research Achievements

Accumulating evidence suggests that mesenteric lymph nodes (MLNs) play important roles in gut-tropic Th17 cell generation, although it is still unclear if MLNs are involved in the pathogenesis of small intestinal inflammation. To address this issue, we analyzed the roles of both MLNs and Peyer’s patches (PPs) by evaluating MLN- or PP-deficient mice in an experimental model of small intestinal inflammation. MLNs, but not PPs, were essential for the pathogenesis of the intestinal inflammation, in particular the accumulation and infiltration of Th17 cells. Furthermore, MLN removal led to a significantly reduced number of peripheral α4β7+ CD4+ effector memory T (TEM) cells under normal conditions, suggesting that MLNs may play a role in maintaining the number of gut-tropic Th17-TEM cells circulating in the blood. Taken together, the present study highlights the important role of MLNs in contributing to the pathogenesis of small intestinal inflammation.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (38 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (4 results) Journal Article (17 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 17 results,  Open Access: 8 results,  Acknowledgement Compliant: 5 results) Presentation (16 results) (of which Int'l Joint Research: 5 results,  Invited: 1 results) Remarks (1 results)

  • [Int'l Joint Research] University of Perugia(Italy)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] University of Hawaii(U.S.A.)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] La Jolla Institute/University of Illinois(米国)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] University of Hawaii/Texas Medical Center(米国)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] TRAF2 and TRAF5 associated with the signal transducing receptor gp130 limit IL-6-driven transphosphorylation of JAK1 through the inhibition of proximal JAK-JAK interaction.2018

    • Author(s)
      Kimura M, Nagashima H, Okuyama Y, Ishii N, and So T
    • Journal Title

      Int. Immunol

      Volume: - Issue: 7 Pages: 219-299

    • DOI

      10.1093/intimm/dxy029

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TNF receptor associated factor 5 controls oncostatin M-mediated lung inflammation.2018

    • Author(s)
      Machiyama T, So T, Okuyama Y, Kobayashi S, Phung HT, Asao A, Harigae H, Ishii N.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: - Issue: 3 Pages: 544-550

    • DOI

      10.1016/j.bbrc.2018.03.186

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] GITR cosignal in ILC2s controls allergic lung inflammation.2018

    • Author(s)
      Nagashima H, Okuyama Y, Fujita T, Takeda T, Motomura Y, Moro K, Hidaka T, Omori K, Sakurai T, Machiyama T, Ndhlovu LC, Riccardi C, So T, Ishii N.
    • Journal Title

      J Allergy Clin Immunol.

      Volume: - Issue: 5 Pages: 1939-1943.e8

    • DOI

      10.1016/j.jaci.2018.01.028

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Inflammatory responses induce an identity crisis of alveolar macrophages, leading to pulmonary alveolar proteinosis.2017

    • Author(s)
      Ebina-Shibuya R, Matsumoto M, Kuwahara M, Jang KJ, Sugai M, Ito Y, Funayama R, Nakayama K, Sato Y, Ishii N, Okamura Y, Kinoshita K, Kometani K, Kurosaki T, Muto A, Ichinose M, Yamashita M, Igarashi K.
    • Journal Title

      The Journal of biological chemistry

      Volume: 292 Issue: 44 Pages: 18098-18112

    • DOI

      10.1074/jbc.m117.808535

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ER Stress Protein CHOP Mediates Insulin Resistance by Modulating Adipose Tissue Macrophage Polarity2017

    • Author(s)
      Suzuki T, Gao J, Ishigaki Y, Kondo K, Sawada S, Izumi T, Uno K, Kaneko K, Tsukita S, Takahashi K, Asao A, Ishii N, Imai J, Yamada T, Oyadomarai S, Katagiri H
    • Journal Title

      Cell Rep

      Volume: 18 Issue: 8 Pages: 2045

    • DOI

      10.1016/j.celrep.2017.01.076

    • NAID

      120007001421

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] TNF superfamily receptor OX40 triggers invariant NKT cell pyroptosis and liver injury2017

    • Author(s)
      Lan P, Fan Y, Zhao Y, Lou X, Monsour HP, Zhang X, Choi Y, Dou Y, Ishii N, Ghobrial RM, Xiao X, Li XC
    • Journal Title

      J Clin Invest.

      Volume: 127 Issue: 6 Pages: 2222-2234

    • DOI

      10.1172/jci91075

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] CD103+ CD11b- salivary gland dendritic cells have antigen cross-presenting capacity.2017

    • Author(s)
      Lu L, Tanaka Y, Ishii N, Sasano T, Sugawara S
    • Journal Title

      Eur J Immunol

      Volume: 47 Issue: 2 Pages: 305-313

    • DOI

      10.1002/eji.201646631

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oral CD103-CD11b+ classical dendritic cells present sublingual antigen and induce Foxp3+ regulatory T cells in draining lymph nodes2017

    • Author(s)
      Tanaka Y, Nagashima H, Bando K, Lu L, Ozaki A, Morita Y, Fukumoto S, Ishii N, Sugawara S
    • Journal Title

      Mucosal Immunol

      Volume: 10 Issue: 1 Pages: 79-90

    • DOI

      10.1038/mi.2016.46

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Apurinic/apyrimidinic endonuclease 1/redox factor-1 (Ape1/Ref-1) modulates antigen presenting cell-mediated T helper cell type 1 responses2016

    • Author(s)
      Akhter N, Takeda Y, Nara H, Araki A, Ishii N, Asao N, Asao H
    • Journal Title

      J Biol Chem

      Volume: 291 Issue: 45 Pages: 23672-23680

    • DOI

      10.1074/jbc.m116.742353

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TNFR-Associated Factors 2 and 5 Differentially Regulate the Instructive IL-6 Receptor Signaling Required for Th17 Development2016

    • Author(s)
      Nagashima, H., Okuyama, Y., Hayashi, T., Ishii, N., So, T.
    • Journal Title

      J Immunol

      Volume: 196 Issue: 10 Pages: 4082-4089

    • DOI

      10.4049/jimmunol.1501610

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] OX40 ligand newly expressed on bronchiolar progenitors mediates influenza infection and further exacerbates pneumonia.2016

    • Author(s)
      Hirano T, Kikuchi T, Tode N, Santoso A, Yamada M, Mitsuhashi Y, Komatsu R, Kawabe T, Tanimoto T, Ishii N, Tanaka Y, Nishimura H, Nukiwa T, Watanabe A, Ichinose M.
    • Journal Title

      EMBO Mol Med.

      Volume: 8 Issue: 4 Pages: 422-436

    • DOI

      10.15252/emmm.201506154

    • NAID

      120006845618

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Mesenteric lymph nodes contribute to proinflammatory Th17-cell generation during inflammation of the samall intestine in mice.2016

    • Author(s)
      Kawabe, T., Suzuki, N., Yamaki, S., Sun, S. L., Asao, A., Okuyama, Y., So, T., Iwakura, Y., and Ishii, N.
    • Journal Title

      Eur. J. Immunol.

      Volume: 46 Issue: 5 Pages: 1119-1131

    • DOI

      10.1002/eji.201545907

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TNF receptor-associated factor-2 and -5 differentially regulate the instructive IL-6 receptor signaling that requires for Th17 development2016

    • Author(s)
      Nagashima H, Okuyama Y, Hayashi T, Ishii N, and So T
    • Journal Title

      J Immunol

      Volume: 印刷中

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Local convection-enhanced delivery of an anti-CD40 agonistic monoclonal antibody induces antitumor effects in mouse glioma models.2016

    • Author(s)
      Shoji T, Saito R, Chonan M, Shibahara I, Sato A, Kanamori M, Sonoda Y, Kondo T, Ishii N, and Tominaga T
    • Journal Title

      Neuro-Oncology

      Volume: 印刷中

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] TIGIT marks exhausted T cells, correlates with disease progression, and serves as target for immune restoration in HIV and SIV infection2016

    • Author(s)
      Chew GM, Fujita T, Webb GM, Burwitz BJ, Wu HL, Reed JS, Hammond KB, Clayton KL, Ishii N, Abdel-Mohsen M, Liegler T, Mitchell BI, Hecht FM, Ostrowski M, Shikuma CM, Hansen SG, Maurer M, Korman AJ, Deeks SG, Sacha JB, Ndhlovu LC.
    • Journal Title

      PLoS Pathol

      Volume: 12 Issue: 1 Pages: e1005349-e1005349

    • DOI

      10.1371/journal.ppat.1005349

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TNF Receptor-Associated Factor (TRAF) Signaling Network in CD4<sup>+</sup> T-Lymphocytes2015

    • Author(s)
      Takanori So, Hiroyuki Nagashima, Naoto Ishii
    • Journal Title

      The Tohoku Journal of Experimental Medicine

      Volume: 236 Issue: 2 Pages: 139-154

    • DOI

      10.1620/tjem.236.139

    • NAID

      130005075699

    • ISSN
      0040-8727, 1349-3329
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CD40/CD40L expression correlates with the survival of patients with glioblastomas and an augmentation in CD40 signaling enhances the efficacy of vaccinations and prolongs survival in intracranial glioma- and glioma-initiating cell-isografted tumor models2015

    • Author(s)
      Chonan M, Saito R, Shoji T, Shibahara I, Kanamori M, Sonoda Y, Watanabe M, Kikuchi T, Ishii N, and Tominaga T
    • Journal Title

      Neuro-Oncology

      Volume: 17 Issue: 11 Pages: 1453-1462

    • DOI

      10.1093/neuonc/nov090

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] TRAF2 and TRAF5 binding to the signal transducing receptor gp130 inhibit JAK1 activation in the IL-6-receptor signaling complex2017

    • Author(s)
      Masanobu Kimura, Hiroyuki Nagashima, Naoto Ishii, Takanori So
    • Organizer
      日本免疫学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Early activation of group 2 innate lymphoid cells in the lung is critically controlled by the TNFR superfamily molecule GITR2017

    • Author(s)
      Takanori So, Hiroyuki Nagashima, Yuko Okuyama, Yasutaka Motomura, Kazuyo Moro, Lishomwa C. Ndhlovu, Carlo Riccardi, Naoto Ishii
    • Organizer
      日本免疫学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] A new regulator of OX40 co-signaling controls autoimmune neuroinflammation mediated by CD4+ T cells2017

    • Author(s)
      Yuko Okuyama, Hiroyuki Nagashima, Masuko Ushio-Fukao, Michael Croft, Naoto Ishii, Takanori So
    • Organizer
      日本免疫学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] TNF receptor-associated factors 5 expressed in non-hematopoietic cells augments acute colonic damage induced by dextran sulfate2017

    • Author(s)
      HAI T PHUNG, Hiroyuki Nagashima, Yuko Okuyama, Shuhei Kobayashi, Atsuko Asao, Naoto Ishii, Takanori So
    • Organizer
      日本免疫学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] A novel regulatory role for TRAF2 and TRAF5 in the IL-6-driven Th17 development.2017

    • Author(s)
      NAGASHIMA Hiroyuki, OKUYAMA Yuko, HAYASHI Takaya, ISHII Naoto, SO Takanori
    • Organizer
      2017 Japan-NIH Joint Symposium
    • Place of Presentation
      星陵オーディトリアム、仙台
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] TRAF2 and TRAF5 have redundant but unequal inhibitory roles in Th17 differentiation mediated by IL-62016

    • Author(s)
      NAGASHIMA Hiroyuki, OKUYAMA Yuko, HAYASHI Takaya, ISHII Naoto, SO Takanori
    • Organizer
      45th Annual Meeting of the Japanese Society for Immunology
    • Place of Presentation
      沖縄コンベンションセンター、宜野湾
    • Year and Date
      2016-12-05
    • Related Report
      2016 Annual Research Report
  • [Presentation] CD4+ T cell-intrinsic TRAF5 negatively regulates Th17 cell-dependent experimental autoimmune encephalomyelitis2016

    • Author(s)
      Hiroyuki Nagashima, Yuko Okuyama, Takaya Hayashi, Atsuko Asao, Takeshi Kawabe, Satoshi Yamaki, Hiroyasu Nakano, Michael Croft, Naoto Ishii, Takanori So
    • Organizer
      International congress of immunology (ICI) 2016
    • Place of Presentation
      Melbourne, Australia
    • Year and Date
      2016-08-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] International Congress of Immunology 20162016

    • Author(s)
      So, T., H. Nagashima, Y. Okuyama, T. Hayashi, A. Asao, T. Kawabe, S. Yamaki, H. Nakano, M. Croft, N. Ishii.
    • Organizer
      TRAF adaptors limit IL-6 receptor signaling through an unexpected binding to the signaling transducer receptor gp130
    • Place of Presentation
      Melbourne, Australia
    • Year and Date
      2016-08-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Traf2とTraf5を介したインターロイキン6(IL-6)シグナル制御2016

    • Author(s)
      長島宏行、石井直人
    • Organizer
      第5回 Multidisciplinary meeting on atherosclerosis
    • Place of Presentation
      仙台トラストシティ カンファレンスルーム、宮城県仙台市
    • Year and Date
      2016-01-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] Role of mesenteric lymphnodes in CD4 T cell homeostasis2015

    • Author(s)
      Naoto Ishii
    • Organizer
      1st Symposium of Creation and Future Trends in Food and Agricultural Immunology
    • Place of Presentation
      Multimedia Education and Research Complex, Tohoku University, Miyagi、Sendai
    • Year and Date
      2015-12-12
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] IQGAP1 regulates OX40 co-signaling in CD4+ T cells2015

    • Author(s)
      奥山祐子、長島宏行、Masuko Ushio-Fukai、Michael Croft、石井直人、宗孝紀
    • Organizer
      第44回日本免疫学会学術集会
    • Place of Presentation
      札幌コンベンションセンター、北海道札幌市
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] TRAF2 and TRAF5 limit the differentiation of Th17 cells mediated by IL-62015

    • Author(s)
      長島宏行、奥山祐子、林隆也、石井直人、宗孝紀
    • Organizer
      第44回日本免疫学会学術集会
    • Place of Presentation
      札幌コンベンションセンター、北海道札幌市
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] OX40-mediated susceptibility to imiquimod-induced psoriasis-like skin inflammation is dependent on IL-132015

    • Author(s)
      浅尾敦子、藤田剛、宗孝紀、星野友昭、石井直人
    • Organizer
      第44回日本免疫学会学術集会
    • Place of Presentation
      札幌コンベンションセンター、北海道札幌市
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] Hepatocyte growth factor-regulated tyrosine kinase substrate is required for T cell development and survival2015

    • Author(s)
      鈴木信、村田和子、奥山祐子、浅尾敦子、宗孝紀、田中伸幸、石井直人
    • Organizer
      第44回日本免疫学会学術集会
    • Place of Presentation
      札幌コンベンションセンター、北海道札幌市
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] Oral classical dendritic cells induce sublingual antigen-specific regulatory T cells in draining lumph nodes2015

    • Author(s)
      田中志典、長島宏行、石井直人、菅原俊二
    • Organizer
      第44回日本免疫学会学術集会
    • Place of Presentation
      札幌コンベンションセンター、北海道札幌市
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] Investigating the Role of the Immune Checkpoint Receptor TIGIT in T cells during HIV Disease Progression and as Target for Immune Restoration2015

    • Author(s)
      Glen M. Chew, Tsuyoshi Fujita, Gabriela Webb, Benjamin J. Burwitz, Kiera L. Clayton, Naoto Ishii, Mohamed Abdel-Mohsen, Teri Liegler, Fredrick M. Hecht, Mario Ostrowski, Mark Maurer, Alan J. Korman, Steven G. Deeks, Jonah B. Sacha and Lishomwa C. Ndhlovu
    • Organizer
      8th Conference of International AIDS association
    • Place of Presentation
      Vancourver, Canada
    • Year and Date
      2015-07-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Remarks] 東北大学大学院医学系研究科免疫学分野

    • URL

      http://www.immunol.med.tohoku.ac.jp/

    • Related Report
      2015 Annual Research Report

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Published: 2015-04-16   Modified: 2022-10-07  

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