期刊
JOURNAL OF AUTOIMMUNITY
卷 78, 期 -, 页码 92-100出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jaut.2016.12.010
关键词
Systemic lupus erythematosus; Triggering receptor expressed on myeloid; cells-1; Ipr mice; B cell-activating factor
类别
资金
- Ministry of Science and Technology, ROC (MOST) [103-2320-B-010-039-MY3, 104-2321-B-010-012]
- Ministry of Education, ROC
- Tri-Service General Hospital
- National Defense Medical Center [TSGHC-C103-062, TSGH-104-057]
- Professor Tsuei-Chu Mong Merit Scholarship
- Taipei City Hospital, Taiwan
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 B6.1pr 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. (C) 2017 Elsevier Ltd. All rights reserved.
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