The role of the TRIM family in systemic lupus erythematosus

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K16157
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Yokohama City University
• Principal Investigator: KAMIYAMA Reikou 横浜市立大学, 医学研究科, 客員研究員 (10739527)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 全身性エリテマトーデス / TRIMファミリー

Outline of Final Research Achievements

Although TRIM proteins and related molecules are expected to be involved in a complex manner in systemic lupus erythematosus (SLE), the direct relationship between SLE pathogenesis and TRIM proteins remains unclear. In this study, we generated Trim39 knockout mice and analyzed the immunological role of TRIM39. We found that Trim39-/- mice had significantly larger thymus and spleen weights and a significantly higher number of spleen cells compared to wild-type mice. The expression of STAT1 was significantly upregulated in the B cells of Trim39-/- mice compared to wild-type mice, and the expression of IL-1 was significantly upregulated in the blood of Trim39-/- mice compared to wild-type mice. Trim39-/- mice had significantly higher levels of IL-27 and significantly lower levels of IgG1 and IgA in blood. The amount of IgA in feces was also significantly lower and DSS-induced enteritis was more severe in Trim39-/- mice.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

TRIMファミリーは自然免疫と獲得免疫の両方において様々な役割を担っていることを示す様々な基礎的な報告がみられるが，SLEを含め膠原病疾患において病態への関与を示した報告はまだ少ない．本研究ではTRIM39の免疫学的な機能が明らかになった．SLEの病因が不明であることから根本的な治療はまだなく，ステロイドや免疫抑制薬による治療に依存している．今回の研究結果はTRIM39とその関連分子を標的とした全身性自己免疫疾患の新規治療薬の開発につながる可能性がある．