Novel therapeutic strategies for Sjogren's syndrome targeting Toll-like receptors.

2021 Fiscal Year Final Research Report

• Project/Area Number: 18H03003
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Kyushu University
• Principal Investigator: Moriyama Masafumi 九州大学, 歯学研究院, 助教 (20452774)
• Co-Investigator(Kenkyū-buntansha): 中村 誠司 九州大学, 歯学研究院, 教授 (60189040) ; 三宅 健介 東京大学, 医科学研究所, 教授 (60229812) ; 坪井 洋人 筑波大学, 医学医療系, 講師 (80580505)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: シェーグレン症候群 / Toll様受容体 / 単球/マクロファージ

Outline of Final Research Achievements

Recent studies suggest that Toll like receptors (TLRs) play an important role in the initiation of autoimmune diseases. In this study, we addressed to identify the disease-associated TLR related molecules in Sjogren’s syndrome (SS), and then examined both expression and function of those molecules. DNA microarray and PCR validated the up-regulation of TLR8 in SS compared with chronic sialadenitis. TLR8 is reported to recognize viral RNA and self-RNA and promote the innate immune responses via TNF-α production. Immunofluorescence double staining and flow cytometry analysis confirmed that the expression of TLR8 almost merged with that of the monocyte/macrophage marker CD68. In vitro examination of human monocyte cell line (U937) by stimulation of TLR8 agonist, concentration of TNF-α in TLR8 knock-in U937 was significantly higher than that in untreated U937 and TLR8 KO U937.. In conclusion, TLR8+ monocyte/macrophage via TNF-α secretion might be involved in the pathogenesis of SS.

Free Research Field

口腔外科学

Academic Significance and Societal Importance of the Research Achievements

現時点ではSSの根治的治療はいまだなく、対症療法のみである。一部の自己免疫疾患では分子標的治療薬が開発され、良好な治療成績が報告されているが、SSでは有効性が低い。これは、SSの病態には様々なサイトカインが関与していることが原因の一つとして推察される。よって本研究により、TLRといった免疫機構の上流の分子を制御することが可能となれば、SSによる腺外症状やドライマウスの改善に寄与できる。