2018 Fiscal Year Final Research Report
Multidirectional investigation to elucidate an effector site of HTLV-1 and molecular machinery in Sjogren's syndrome
| Project/Area Number |
16K09899
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Collagenous pathology/Allergology
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| Research Institution | Nagasaki University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
清水 俊匡 長崎大学, 病院(医学系), 助教 (40770467)
高谷 亜由子 長崎大学, 病院(医学系), 医員 (90821380)
川上 純 長崎大学, 医歯薬学総合研究科(医学系), 教授 (90325639)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | シェーグレン症候群 / HTLV-1 |
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| Outline of Final Research Achievements |
Expression of HTLV-1 bZIP factor (HBZ), tax and relevant molecules in labial salivary glands (LSGs) from patients with Sjogren's syndrome (SS) was examined by in situ hybridization (ISH)and immunohistochemistry. In LSGs from an adult T-cell leukemia (ATL) patient and HTLV-1-associated myelopathy (HAM)SS patients, both HBZ and tax signals were detected in infiltrating mononuclear cells (MNCs) and ducts, and HBZ and tax were dominantly expressed in MNCs of HAMSS, respectively. HBZ was dominantly observed in LSGs from HTLV-1 asymptomatic carrier (AC)-SS patients. Although Foxp3 expression was observed in LSG MNCs of all of the SS patients, the ATL patient's expression was significantly greater than that of the AC-SS (p<0.01) and HTLV-1-seronegative SS (p<0.01) patients. p65 was expressed in LSG MNC nuclei from all SS patients and co-expressed with Foxp3. These results suggest that HBZ-mediated Foxp3 expression is in part associated with the pathogenesis of HTLV-1-seropositive SS.
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| Free Research Field |
膠原病分野
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| Academic Significance and Societal Importance of the Research Achievements |
シェーグレン症候群（SS)におけるHTLV-1の関与について、ISHおよび免疫組織検討を行い、ATLとHAMSSでは、浸潤単核球におけるHBZとtaxの発現比率に差がみられた。また、浸潤単核球におけるNF-kB発現はHTLV-I感染に関わらず同等であったが、Foxp3はATLおよびHAMSSに優位であり、HBZ-Foxp3がHTLV-I感染病態により特異的に関与している可能性が示唆された。これまでの研究ではHTLV-1陽性SS唾液腺の遺伝子発現はtaxのみでの検討であったが、HBZとその誘導蛋白Foxp3の発現が明らかとなった。進歩の乏しかったSSとHTLV-1の直接的関連が明確となった。
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