| Project/Area Number |
18K16031
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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 | Hiroshima University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 黄色ブドウ球菌 / ケラチノサイト / アトピー性皮膚炎 / Microbiome / Cell wall protein / 自然免疫 |
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| Outline of Final Research Achievements |
Staphylococcus aureus (S. aureus) is frequently detected in patients with AD and decreased diversity of bacterial flora on the skin surface (dysbiosis) has come to be considered as an important pathogenic factor of AD. We previously demonstrated altered skin immune responses induced by AD skin-derived strains of S. aureus (AD strain) compared to those by standard strains of S. aureus. However, detailed mechanisms underlying S. aureus colonization have not been sufficiently elucidated.
AD strain, exploration of the innate immune responses involving keratinocytes showed that the AD strain was specifically internalized into lysosomes of the keratinocytes, indicating divergent morphological behavior.
Inhibiting the uptake of this AD strain into keratinocyte are expected to represent a therapeutic target in the development of future treatments for AD. We established the assay system for exploring potent compounds of blocking AD strain by using high-throughput imaging system.
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| Academic Significance and Societal Importance of the Research Achievements |
ヒト皮膚表面の細菌叢を構成する細菌・真菌と皮膚免疫の関連性は近年多くの研究が報告されており、我々は、AD患者で効率に検出されるS. aureusに注目し、AD株は特異的な免疫反応を誘導するのではないか？という作業仮説をたて、ランゲルハンス細胞を介した自然免疫および獲得免疫に違いが出ることを見出した。AD皮膚に定着しているS. aureusのコントロールする点に注目した新規治療法の開発の着想を得て、今回S. aureus が最初にコンタクトするケラチノサイトに注目し、自然免疫を軸とした免疫応答を中心にAD株の特徴を捉え、新たな治療戦略への道を拓くことを考えている。
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