Study on the role of Triggering Receptors Expressed on Myeloid cells-1 in systemic lupus erythematosus by using Triggering Receptors Expressed on Myeloid cells-1 knockout mice

• Main Authors: Ssu-Hsuan Chiang, 江思萱
• Other Authors: Kuang-Hui Sun
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/77e9km

碩士 === 國立陽明大學 === 醫學生物技術暨檢驗學系 === 102 === Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease. Patient’s immune system attacks his own cells and tissues and results in inflammation and tissue damage. Patients are characterized by antinuclear antibodies (ANAs) in serum, especially anti-double-strand DNA antibodies (anti-dsDNA). TREM-1 (Triggering Receptors Expressed on Myeloid cells-1) has been demonstrated to synergize with TLR (Toll-Like Receptors) in amplifying the inflammatory response and play an important role in many bacterial infectious diseases and aseptic inflammatory diseases. TREM-1 blockade had been shown to reduce the inflammation in septic mice and mice with collagen-induced arthritis (CIA). Furthermore, levels of soluble form of TREM-1 (sTREM-1) were found elevated in sera of SLE patients. In our preliminary study, TREM-1 expression has increased significantly in spleen of lupus mice (B6.Lpr) and also has a positive correlation with lupus symptoms, suggesting that TREM-1 may be involved in the progression of SLE. In this study, we established TREM-1-/--Lpr mice by breeding B6.Lpr mice with TREM-1-/- mice to investigate the role of TREM-1 in SLE. First, we found the survival rate of TREM-1-/--Lpr mice were significantly lower than control groups. Lupus symptoms of TREM-1-/--Lpr mice became more severe nearly at 42-weeks including spleen weight, lymph node weight, proteinuria level, BUN levels, anti-dsDNA and anti-Sm antibodies titers. WBC and lymphocytes of TREM-1-/--Lpr mice was significantly increased at 24-weeks, but was compensable at the age of 42-weeks. Peripheral immature T cell (CD3+CD4-CD8-T cell) of TREM-1-/--Lpr mice were greatly increased compared to B6.Lpr mice at 42-weeks. Furthermore, myeloid dendritic cells (mDC), plasmacytoid dendritic cells (pDC), plasma cells, T cells, B cells, immature T cells and immature B cells (T1 B) were increased enormously in spleen and lymph node of TREM-1-/--Lpr mice at 42-weeks. In addition, concentrations of BAFF (B-cell activating factor), IFN-, IL-2, IFN-, TNF, IL-4, IL-6, IL-10 and IL-17 were elevated in serum of TREM-1-/--Lpr mice. These data indicated that TREM-1-/--Lpr mice represented more severe clinical symptoms of SLE. Immature T and immature B cells of TREM-1-/--Lpr mice were increased significantly in peripheral blood, spleen and lymph node, suggesting that TREM-1 may modulate the development of autoreactive lymphocytes in SLE.