Molecular mechanisms involved in epicutaneous sensitization

• Project/Area Number: 15H04866
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: National Center for Child Health and Development
• Principal Investigator: Saito Hirohisa 国立研究開発法人国立成育医療研究センター, 副所長室, 副所長 (40130166)
• Co-Investigator(Kenkyū-buntansha): 中江 進 東京大学, 医科学研究所, 准教授 (60450409)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000); Fiscal Year 2017: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
• Keywords: 経皮膚感作 / 皮膚炎 / プロテアーゼ / アレルギー

Outline of Final Research Achievements

It has been shown that epicutaneous sensitization through eczema may be involved in the development of atopic dermatitis and subsequent other allergic diseases. Staphylococcus aureus is known to be colonized especially on the lesional skin of patients with atopic dermatitis and some of those are known to produce protease that may lead barrier dysfunction. Therefore, we sought to elucidate the effect of protease produced by staphylococcus aureus on skin. Consequently, we found that protease from staphylococcus aureus induced skin inflammation accompanied by acanthosis and inflammatory cell infiltration even in the absence of acquired immunity.

Research Products

• [Int'l Joint Research] SIAF(Switzerland)
• [Int'l Joint Research] Stanford University School of Medicine/Department of Pathology(米国)
• [Int'l Joint Research] Cambridge University/MRC Laboratory of Molecular Biology(英国)
• [Int'l Joint Research] SIAF(Switzerland)
• [Int'l Joint Research] Stanford University School of Medicine/Departments of Pathology(米国)
• [Int'l Joint Research] Cambridge/MRC Laboratory of Molecular Biology(英国)
• [Journal Article] The optimal age for epicutaneous sensitization following tape-stripping in BALB/c mice (2018)
  • Author(s): Tamari M, Orimo K, Motomura K, Arae K, Matsuda A, Nakae S, Saito H, Morita H, Matsumoto K
  • Journal Title: Allergology International Volume: 67 Issue: 3 Pages: 380-387
  • DOI: 10.1016/j.alit.2018.01.003
  • NAID: 130007420809
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access
• [Journal Article] Recent advances in understanding the roles of blood platelets in the pathogenesis of allergic inflammation and bronchial asthma (2018)
  • Author(s): Takeda T, Morita H, Saito H, Matsumoto K, Matsuda A
  • Journal Title: Allergology International Volume: 67 Issue: 3 Pages: 326-333
  • DOI: 10.1016/j.alit.2017.11.008
  • NAID: 130007420477
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access
• [Journal Article] IL-25 enhances Th17 cell-mediated contact dermatitis by promoting IL-1b production by dermal dendritic cells (2018)
  • Author(s): Suto H, Nambu A, Morita H, Yamaguchi S, Numata T, Yoshizaki T, Shimura E, Arae K, Asada Y, Motomura K, Kaneko M, Abe T, Matsuda A, Iwakura Y, Okumura K, Saito H, Matsumoto K, Sudo K, Nakae S
  • Journal Title: J Allergy Clin Immunol Volume: In press Issue: 5 Pages: 1500-1509
  • DOI: 10.1016/j.jaci.2017.12.1007
  • Peer Reviewed / Open Access
• [Journal Article] Are both early egg introduction and eczema treatment necessary for primary prevention of egg allergy? (2018)
  • Author(s): Matsumoto K, Mori R, Miyazaki C, Ohya Y, Saito H
  • Journal Title: J Allergy Clin Immunol Volume: In press Issue: 6 Pages: 1997-2001.e3
  • DOI: 10.1016/j.jaci.2018.02.033
• [Journal Article] Two-step egg introduction for prevention of egg allergy in high-risk infants with eczema (PETIT): a randomised, double-blind, placebo-controlled trial. (2017)
  • Author(s): Natsume O, Kabashima S, Nakazato J, Yamamoto-Hanada K, Narita M, Kondo M, Saito M, Kishino A, Takimoto T, Inoue E, Tang J, Kido H, Wong GW, Matsumoto K, Saito H, Ohya Y; PETIT Study Team..
  • Journal Title: Lancet Volume: 389 Issue: 10066 Pages: 276-286
  • DOI: 10.1016/s0140-6736(16)31418-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Regulatory roles of mast cells in imuune responses (2016)
  • Author(s): Morita H, Saito H, Matsumoto K, Nakae S.
  • Journal Title: Semin Immunopathol Volume: 38 Issue: 5 Pages: 623-629
  • DOI: 10.1007/s00281-016-0566-0
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Epicutaneous allergic sensitization by cooperation between allergn protease activity and mechanical skin barrier damage in mice (2016)
  • Author(s): Shimura S, Takai T, Iida H, Maruyama N, Ochi H, Kamijo S, Nishioka I, Hara M, Matsuda A, Saito H, Nakae S, Ogawa H, Okumura K, Ikeda S.
  • Journal Title: J Invest Dermatol Volume: 136 Issue: 7 Pages: 1408-1417
  • DOI: 10.1016/j.jid.2016.02.810
  • Peer Reviewed
• [Journal Article] Subcutaneous Allergic Sensitization to Protease Allergen Is Dependent on Mast Cells but Not IL-33: Distinct Mechanisms between Subcutaneous and Intranasal Routes (2016)
  • Author(s): Kamijo S, Suzuki M, Hara M, Shimura S, Ochi H, Maruyama N, Matsuda A, Saito H, Nakae S, Suto H, Ichikawa S, Ikeda S, Ogawa H, Okumura K, Takai T.
  • Journal Title: J Immunol Volume: 196 Issue: 9 Pages: 3559-3569
  • DOI: 10.4049/jimmunol.1500717
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Platelets constitutively express IL-33 protein and modulate eosinophilic airway inflammation. (2016)
  • Author(s): Takeda T, Unno H, Morita H, Futamura K, Emi-Sugie M, Arae K, Shoda T, Okada N, Igarashi A, Inoue E, Kitazawa H, Nakae S, Saito H, Matsumoto K, Matsuda A.
  • Journal Title: J Allergy Clin Immunol Volume: In Press Issue: 5 Pages: 1395-1403
  • DOI: 10.1016/j.jaci.2016.01.032
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Sera of patients with infantile eosinophilic gastroenteritis showed a specific increase in both thymic stromal lymphopoietin and IL-33 levels (2016)
  • Author(s): Shoda T, Matsuda A, Arai K, Shimizu H, Morita H, Orihara K, Okada N, Narita M, Ohya Y, Saito H, Matsumoto K, Nomura I.
  • Journal Title: J Allergy Clin Immunol. Volume: in press Issue: 1 Pages: 299-303
  • DOI: 10.1016/j.jaci.2015.11.042
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Recent advances in understanding the roles of vascular endothelial cells in allergic inflammation (2016)
  • Author(s): Shoda T, Futamura K, Orihara K, Emi-Sugie M, Saito H, Matsumoto K, Matsuda A.
  • Journal Title: Allergology International Volume: 65 Issue: 1 Pages: 21-29
  • DOI: 10.1016/j.alit.2015.08.001
  • NAID: 130005290335
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access
• [Journal Article] Transepidermal water loss measurement during infancy can predict the subsequent development of atopic dermatitis regardless of filaggrin mutations (2016)
  • Author(s): Horimukai K, Morita K, Narita M, Kondo M, Kabashima S, Inoue E, Sasaki T, Niizeki H, Saito H, Matsumoto K, Ohya Y.
  • Journal Title: Allergology International Volume: 65 Issue: 1 Pages: 103-108
  • DOI: 10.1016/j.alit.2015.09.004
  • NAID: 130005290309
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] IL-25 and IL-33 Contribute to Development of Eosinophilic Airway Inflammation in Epicutaneously Antigen-Sensitized Mice. (2015)
  • Author(s): Morita H, Arae K, Unno H, Toyama S, Motomura K, Matsuda A, Suto H, Okumura K, Sudo K, Takahashi T, Saito H, Matsumoto K, Nakae S.
  • Journal Title: PLoS One. Volume: 10 Issue: 7 Pages: e0134226-e0134226
  • DOI: 10.1371/journal.pone.0134226
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] An Interleukin-33-Mast Cell-Interleukin-2 Axis Suppresses Papain-Induced Allergic Inflammation by Promoting Regulatory T Cell Numbers. (2015)
  • Author(s): Morita H, Arae K, Unno H, Miyauchi K, Toyama S, Nambu A, Oboki K, Ohno T, Motomura K, Matsuda A, Yamaguchi S, Narushima S, Kajiwara N, Iikura M, Suto H, McKenzie AN, Takahashi T, Karasuyama H, Okumura K, Azuma M, Moro K, Akdis CA, Galli SJ, Koyasu S, Kubo M, Sudo K, Saito H, Matsumoto K, Nakae S.
  • Journal Title: Immunity Volume: 43 Issue: 1 Pages: 175-86
  • DOI: 10.1016/j.immuni.2015.06.021
  • NAID: 40020962854
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Measurement of allergen-specific secretory IgA in stool of neonates, infants and toddlers by protection against degradation of immunoglobulins and allergens (2015)
  • Author(s): Norio Kamemura, Miwa Takashima, Hideaki Morita, Kenji Matsumoto, Hiroshi Saito, and Hiroshi Kido.
  • Journal Title: The Journal of Medical Investigation Volume: 62 Issue: 3.4 Pages: 137-144
  • DOI: 10.2152/jmi.62.137
  • NAID: 130005099155
  • ISSN: 1343-1420, 1349-6867
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Total serum IgE level influences oral food challenge tests for IgE-mediated food allergies. (2015)
  • Author(s): Horimukai K, Hayashi K, Tsumura Y, Nomura I, Narita M, Ohya Y, Saito H, Matsumoto K.
  • Journal Title: Allergy Volume: 70 Issue: 3 Pages: 334-7
  • DOI: 10.1111/all.12562
  • Peer Reviewed
• [Journal Article] Global DNA hypomethylation coupled to cellular transformation and metastatic ability. (2015)
  • Author(s): Funaki S, Nakamura T, Nakatani T, Umehara H, Nakashima H, Okumura M, Oboki K, Matsumoto K, Saito H, Nakano T.
  • Journal Title: FEBS lett. Volume: 589 Issue: 24PartB Pages: 4053-60
  • DOI: 10.1016/j.febslet.2015.11.020
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of a polyI:C-inducible membrane protein that participates in dendritic cell-mediated natural killer cell activation. (2015)
  • Author(s): Ebihara T, Azuma M, Oshiumi H, Kasamatsu J, Iwabuchi K, Matsumoto K, Saito H, Taniguchi T, Matsumoto M, Seya T.
  • Journal Title: J Exp Med Volume: 212 Issue: 8 Pages: 1337-1337
  • DOI: 10.1084/jem.2009157307012015c
  • NAID: 120002722561
  • Peer Reviewed