2018 Fiscal Year Final Research Report
Elucidation of pathomechanisms and Development of new treatment strategies for aseptic pustuloses
| Project/Area Number |
15H04886
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Fujita Health University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
藤猪 英樹 琉球大学, 医学(系)研究科(研究院), 准教授 (50356250)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | 膿疱症 / 膿疱性乾癬 / IL36RN / CARD14 / IL-36受容体拮抗因子欠損症 / CARD14関連乾癬 / AP1S3 / CXCR2阻害薬 |
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| Outline of Final Research Achievements |
We showed that AP1S3 was not causative gene of pustuloses in Japanese. In addition, we found an autosomal dominant pedigree of generalized pustular psoriasis (GPP) associated with a CARD14 mutation, which was previously reported in a patient with pityriasis rubra pilaris. We also found a previously unreported homozygous IL36RN missense mutation in the two siblings with. Moreover, we established imiquimod (IMQ)-induced psoriasiform dermatitis in Il36rn knock out mice by topical application of IMQ to the back skin. We then treated IMQ-induced GPP model Il36rn/ mice with the anti-IL-17a antibody and the CXCR2 inhibitor. The anti-IL-17a antibody and the CXCR2 antagonist attenuated the clinical symptoms.
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| Free Research Field |
炎症性角化症
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| Academic Significance and Societal Importance of the Research Achievements |
膿疱症の病因について、さらに解明された。具体的には、AP1S3は欧州の膿疱症には関連がある遺伝子であるが、日本人の膿疱症では無関係であることが明らかになった。日本人の膿疱性乾癬の病的変異を明らかにした。具体的には、CARD14c.349+1G>Aでは毛孔性紅色粃糠疹のみならず、GPPの病因であることを解明し、常染色体優勢遺伝のGPPの家系を日本で初めて明らかにした。さらにIL36RN新規遺伝子変異c.125T>Aを晃にした。さらに、膿疱性乾癬の治療薬として好中球遊走を抑制するCXCR2阻害薬が有効である可能性を提示した。
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