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Pathological analysis of skin fibrosis, focused on type 2 innate immune lymphoid cells

Research Project

Project/Area Number 24659520
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Dermatology
Research InstitutionChiba University

Principal Investigator

KAMBE Naotomo  千葉大学, 医学研究院, 准教授 (50335254)

Co-Investigator(Kenkyū-buntansha) NAKAE Susumu  東京大学, 医科 学研究所, 准教授 (60450409)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2012: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Keywords皮膚炎症・再生学 / 皮膚硬化性病変 / IL-33
Research Abstract

We have studied the mechanism of cryopyrin-associated periodicsyndrome (CAPS), in which an active mutant of NLRP3 spontaneously forms inflammasome andinduces hyper-production of IL-1β. This study led us to focus on the pivotal role of IL-1 in skindiseases. Recently, people pay attention to another IL-1 family molecule, IL-33, because IL-33released from damaged cells in inflammation is critically involved in inflammatory response by aproduction of Th2 cytokines and a degranulation of mast cells. In addition, IL-33 induces a largeamount of Th2 cytokine production from innate lymphoid cells (ILCs). ILCs are newly identifiedlymphoid lineage cells, keep haematopoietic stem cell markers and are present in the mesentericfat-associated lymphoid clusters.
Interestingly, the structure of mesenteric fat-associated lymphoid clusters shares thesimilar feature with that of aggregated clusters of lymphoid cells in subcutaneous fat in localizedscleroderma. Also serum IL-33 is reported to be elevated in scleroderma and serum levels of IL-33is well correlated with the severity of cutaneous sclerosis in scleroderma. Therefore, we studied therole of IL-33 in bleomycin-induced scleroderma murine model by comparing the effect in IL-33deficient mice and wild type mice.
Six weeks after bleomycin-treatment, we obtained localized cutaneous sclerosisaccompanied with increased skin fibrosis in wild type mice. However, lymphoid cell infiltrationwas not observed in the skin lesion. Unfortunately, the cutaneous sclerosis including histologicalfeatures in IL-33 deficient mice was almost identical to that in wild type mice. We concluded from these results that we should verify the cutaneous role of IL-33 by focusing on Th2 immuneresponse, and now we are establishing such a model to confirm it.

Report

(2 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • Research Products

    (22 results)

All 2013 2012

All Journal Article (22 results) (of which Peer Reviewed: 6 results)

  • [Journal Article] Dok adaptors play anti-inflammatory roles in pulmonary homeostasis.2013

    • Author(s)
      Mashima R, Arimura S, Kajikawa S, Oda H, Nakae S, Yamanashi Y.
    • Journal Title

      Genes to Cells

      Volume: 18 Issue: 1 Pages: 56-65

    • DOI

      10.1111/gtc.12016

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of Interleukin-33 in Innate-Type Immune Cells in Allergy2013

    • Author(s)
      Nakae S, Morita H, Ohno T, Arae K, Matsumoto K, Saito H
    • Journal Title

      Allergology International

      Volume: 62 Issue: 1 Pages: 13-20

    • DOI

      10.2332/allergolint.13-RAI-0538

    • NAID

      130004477181

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] ST2 Requires Th2-, but Not Th17-, Type Airway Inflammation in Epicutaneously Antigen-Sensitized Mice2012

    • Author(s)
      Morita H, Arae K, Ohno T, Kajiwara N, Oboki, K, Matsuda A, Suto H, Okumura K, Sudo K, Takahashi T, Matsumoto K, Nakae, S
    • Journal Title

      Allergology International

      Volume: 61 Issue: 2 Pages: 265-273

    • DOI

      10.2332/allergolint.11-OA-0379

    • NAID

      130004477129

    • ISSN
      1323-8930, 1440-1592
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Epithelial cell-derived IL-25, but not Th17 cell-derived IL-17 or IL-17F, is crucial for murine asthma2012

    • Author(s)
      Suzukawa M, Morita H, Nambu A, Arae K, Shimura E, Shibui A, Yamaguchi S, Suzukawa K, Nakanishi W, Oboki K, Kajiwara N Ohno T, Ishii A, Korner H, Cua DJ, Suto H, Yoshimoto T, Iwakura Y, Yamasoba T, Ohta K, Sudo K, Saito H, Okumura K, Broide DH, Matsumoto K, Nakae S
    • Journal Title

      J Immunol

      Volume: 189 Pages: 3641-52

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Interleukin-33 in allergy.2012

    • Author(s)
      Ohno T, Morita H, Arae K, Matsumoto K, Nakae S.
    • Journal Title

      Allergy.

      Volume: 67 Issue: 10 Pages: 1203-14

    • DOI

      10.1111/all.12004

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] 「皮膚免疫学-免疫臓器としての意義と病態」皮膚と自己炎症性機序による肉芽腫性疾患2012

    • Author(s)
      中野倫代,神戸直智
    • Journal Title

      医学のあゆみ

      Volume: 242 Pages: 791-4

    • Related Report
      2012 Final Research Report
  • [Journal Article] NLRP3インフラマソームを介したマスト細胞の活性化2012

    • Author(s)
      神戸直智,中村悠美
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 58 Pages: 560-4

    • Related Report
      2012 Final Research Report
  • [Journal Article] IL-33と慢性アレルギー炎症2012

    • Author(s)
      大野建州,東みゆき,中江進
    • Journal Title

      実験医学

      Volume: 30 Pages: 918-5

    • Related Report
      2012 Final Research Report
  • [Journal Article] IL-33によるマスト細胞の活性化2012

    • Author(s)
      新江賢,大野建州,森田英明,松本健治,中江進
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 57 Pages: 625-3

    • Related Report
      2012 Final Research Report
  • [Journal Article] IL-33によるマスト細胞・好塩基球の活性化とアレルギー疾患2012

    • Author(s)
      森田英明,新江賢,大野建州,松本健治,中江進
    • Journal Title

      炎症と免疫

      Volume: 20 Pages: 340-50

    • Related Report
      2012 Final Research Report
  • [Journal Article] IL-33とアレルギー2012

    • Author(s)
      大野建州,森田英明,新江賢,松本健治,中江進
    • Journal Title

      IgE practice in asthma

      Volume: 6 Pages: 11-17

    • NAID

      40022317104

    • Related Report
      2012 Final Research Report
  • [Journal Article] IL-33による慢性アレルギー炎症2012

    • Author(s)
      大野建州,森田英明,新江賢,松本健治,中江進
    • Journal Title

      アレルギーの臨床

      Volume: 32 Pages: 918-23

    • Related Report
      2012 Final Research Report
  • [Journal Article] IL-25,IL-33と自然リンパ球~感染防御,アレルギー疾患へのかかわり~2012

    • Author(s)
      大野建州,東みゆき,中江進
    • Journal Title

      実験医学

      Volume: 30 Pages: 3062-71

    • Related Report
      2012 Final Research Report
  • [Journal Article] Epithelial cell-derived IL-25, but not Th17 cell-derived IL-17 or IL-17F, is crucial for murine asthma.2012

    • Author(s)
      Suzukawa M, Morita H, Nambu A, 他22名, Nakae S.
    • Journal Title

      J Immunol.

      Volume: 189 Pages: 3641-52

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 「皮膚免疫学-免疫臓器としての意義と病態」皮膚と自己炎症性機序による肉芽腫性疾患.2012

    • Author(s)
      中野倫代,神戸直智.
    • Journal Title

      医学のあゆみ.

      Volume: 242 Pages: 791-4

    • Related Report
      2012 Annual Research Report
  • [Journal Article] NLRP3インフラマソームを介したマスト細胞の活性化.2012

    • Author(s)
      神戸直智,中村悠美.
    • Journal Title

      臨床免疫・アレルギー科.

      Volume: 58 Pages: 560-4

    • Related Report
      2012 Annual Research Report
  • [Journal Article] IL-33と慢性アレルギー炎症.2012

    • Author(s)
      大野建州,東みゆき,中江 進.
    • Journal Title

      実験医学.

      Volume: 30 Pages: 918-5

    • Related Report
      2012 Annual Research Report
  • [Journal Article] IL-33によるマスト細胞の活性化.2012

    • Author(s)
      新江 賢,大野建州,森田英明,松本健治,中江 進.
    • Journal Title

      臨床免疫・アレルギー科.

      Volume: 57 Pages: 625-3

    • Related Report
      2012 Annual Research Report
  • [Journal Article] IL-33によるマスト細胞・好塩基球の活性化とアレルギー疾患.2012

    • Author(s)
      森田英明,新江賢,大野建州,松本健治,中江 進.
    • Journal Title

      炎症と免疫

      Volume: 20 Pages: 340-50

    • Related Report
      2012 Annual Research Report
  • [Journal Article] IL-33とアレルギー.2012

    • Author(s)
      大野建州,森田英明,新江賢,松本健治,中江 進
    • Journal Title

      IgE practice in asthma.

      Volume: 6 Pages: 11-17

    • NAID

      40022317104

    • Related Report
      2012 Annual Research Report
  • [Journal Article] IL-33による慢性アレルギー炎症.2012

    • Author(s)
      大野建州,森田英明,新江賢,松本健治,中江 進.
    • Journal Title

      アレルギーの臨床.

      Volume: 32 Pages: 918-23

    • Related Report
      2012 Annual Research Report
  • [Journal Article] IL-25,IL-33と自然リンパ球〜感染防御,アレルギー疾患へのかかわり〜.2012

    • Author(s)
      大野建州,東みゆき,中江 進.
    • Journal Title

      実験医学

      Volume: 30 Pages: 3062-71

    • Related Report
      2012 Annual Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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