Mechanism of skin eruption due to ultraviolet rays in hydroa vacciniforme patients

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16341
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Okayama University
• Principal Investigator: HIRAI YOJI 岡山大学, 大学病院, 助教 (10756068)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 種痘様水疱症 / EBウイルス / 非バイアス次世代TCRレパトア解析 / γδT細胞 / 蚊刺過敏症

Outline of Final Research Achievements

Hydroa vacciniforme (HV) is a rare photosensitivity disorder of childhood associated with Epstein-Barr virus (EBV)+　T-cell infiltration, although the precise mechanism of eruption due to UV rays remains unknown. There are also many unclear pathomechanisms in cases of systemic HV (sHV), which shows systemic symptoms such as fever, blood abnormalities, and malignant changes. The present study revealed that C-X-C motif chemokine 12 (CXCL12) is involved in the migration of EB virus-infected γδ T cells to the skin, and that macrophage-derived chemokines (MDCs) are released from epidermal keratinocytes by ultraviolet rays to obtain proliferative ability. T-cell receptor (TCR) repertoire analysis using next-generation sequencing showed that peripheral tissue type EBV＋Vδ1 could selectively infiltrate skin lesions. Furthermore, the percentages of coexpression of CD16 and/or CD56 by T-cell large granular lymphocytes might serve as a surrogate marker for the tumor burden in sHV patients.

Free Research Field

ウイルス感染症

Academic Significance and Societal Importance of the Research Achievements

種痘様水疱症は稀な小児の光線過敏症で、通常は遮光や対症療法で自然軽快するが、発熱や血液学的検査異常を伴い、慢性活動性EBウイルス感染症の合併例が多い全身型種痘様水疱症への移行例や全身型種痘様水疱症の成人/高齢発症例が存在する。全身型種痘様水疱症は確立した治療法が無く、また東南アジア・中南米などの限られた地区で報告されており、病態解析と新治療薬の開発が急がれる。本研究では、種痘様水疱症の皮疹形成機序、また全身型種痘様水疱症における腫瘍量の代用マーカーを探求し意義あるものと考える。