| Project/Area Number |
18K16022
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53050:Dermatology-related
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| Research Institution | University of Yamanashi |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | Stevens-Johnson症候群 / 中毒性表皮壊死症 / 好中球 / NETs / NETosis / 抗菌ペプチド / 表皮細胞 / SJS / TEN / 重症薬疹 / スティーブンス・ジョンソン症候群 / 表皮細胞死 / ネクロプトーシス / LL-37 |
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| Outline of Final Research Achievements |
Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are life-threatening mucocutaneous adverse drug reactions characterized by massive epidermal detachment. We found a mechanism by which neutrophils trigger inflammation during early phases of SJS/TEN. Skin-infiltrating neutrophils undergoing neutrophil extracellular traps (NETs) released LL-37, an antimicrobial peptide, which induced formyl peptide receptor 1 (FPR1) expression by keratinocytes. FPR1-expression rendered keratinocytes vulnerable to necroptosis. Necroptotic keratinocytes further released LL-37 to induce FPR1 expression on surrounding keratinocytes, which likely amplified the necroptotic response. This pathway may be leveraged to establish both early diagnostic markers and therapeutic targets.
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| Academic Significance and Societal Importance of the Research Achievements |
薬疹は内服薬や注射薬などの投薬により発症し、全身の皮膚粘膜に障害をきたす。特に重症薬疹である SJS/TEN は、全身の表皮壊死に加え多臓器障害を伴い、ときに致死的となる。仮に救命できても、失明など重篤な後遺症を残す患者は多い。薬剤による健康障害としては、重症薬疹が最多である (医薬品医療機器総合機構の集計)。
本来、治療目的で行われる投薬による医原性疾患であること、老若男女を問わず発症しうること、急激な転機で致死的になり得ることから、その病態解明と治療確立は切迫した課題である。
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