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Title: Triggering receptor expressed on myeloid cells-1 (TREM-1) deficiency augments BAFF production to promote lupus progression.
Authors: Chi-Jui Liu
Chang-Youh Tsai
Ssu-Hsuan Chiang
Shye-Jye Tang
Nien-Jung Chene
Tak Wah Mak
Guang-Huan Sung
Kuang-Hui Sun
Contributors: 國立臺灣海洋大學:生命科學系
Date: 2017
Issue Date: 2018-03-21T03:06:37Z
Publisher: Journal of Autoimmunity
Abstract: Abstract: Sensing of nucleic acids by pattern recognition receptors is the key for the initiation and development of systemic lupus erythematosus (SLE). Triggering receptor expressed on myeloid cells-1 (TREM-1) is a novel innate immune receptor, which can amplify Toll-like receptor (TLR)-induced inflammatory responses. Although patients with lupus exhibit increased serum levels of soluble TREM-1 (sTREM-1), the role of TREM-1 in SLE remains unknown. In current study, we found serum sTREM-1 levels were significantly increased in lupus patients and positively correlated with disease activity. Additionally, diseased B6.lpr mice had elevated TREM-1 in the serum, spleen, and lymph nodes. To investigate the role of TREM-1 in lupus, we established Trem-1−/−.lpr mice. Trem-1−/−.lpr mice exhibited lower survival rates and more severe lupus symptoms, including elevated proteinuria, serum anti-dsDNA antibody levels, renal immune complex depositions and lymphocyte subpopulation expansions in both the spleen and lymph nodes. Besides, Trem-1−/−.lpr mice expressed higher serum B cell-activating factor (BAFF) levels and lymph node dendritic cells (DCs) were the major source of increased BAFF. Activation of membrane-bound TREM-1 could suppress TLR9-induced BAFF expression in bone marrow-derived DCs of B6.lpr mice. Moreover, levels of sTREM-1, which could act as an antagonist of membrane-bound TREM-1, were positively correlated with levels of BAFF in the sera of lupus patients. Our findings suggest a novel modulatory role of TREM-1 in the pathogenesis of SLE. sTREM-1 production is a useful diagnostic marker and a molecular target for combination therapy of lupus.
Relation: 78
Appears in Collections:[Department of Life Science] Periodical Articles

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