title: Triggering receptor expressed on myeloid cells-1 (TREM-1) deficiency augments BAFF production to promote lupus progression.
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.
authors.affiliation: Department of Biotechnology and Laboratory Science in Medicine, VYM Genome Research Center, National Yang-Ming University, Taipei, 112, Taiwan.
authors.forename: Chi-Jui
authors.initials: CJ
authors.lastname: Liu
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, 112, Taiwan.
authors.forename: Chang-Youh
authors.initials: CY
authors.lastname: Tsai
authors.affiliation: Department of Biotechnology and Laboratory Science in Medicine, VYM Genome Research Center, National Yang-Ming University, Taipei, 112, Taiwan.
authors.forename: Ssu-Hsuan
authors.initials: SH
authors.lastname: Chiang
authors.affiliation: Institute of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, 202, Taiwan.
authors.forename: Shye-Jye
authors.initials: SJ
authors.lastname: Tang
authors.affiliation: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, 112, Taiwan.
authors.forename: Nien-Jung
authors.initials: NJ
authors.lastname: Chen
authors.affiliation: The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network, Toronto, Ontario, M5G 2C1, Canada.
authors.forename: Tak Wah
authors.initials: TW
authors.lastname: Mak
authors.affiliation: Division of Urology, Department of Surgery, Tri-Service General Hospital and National Defense Medical Center, Taipei, 114, Taiwan. Electronic address: ghsun@ndmctsgh.edu.tw.
authors.forename: Guang-Huan
authors.initials: GH
authors.lastname: Sun
authors.affiliation: Department of Biotechnology and Laboratory Science in Medicine, VYM Genome Research Center, National Yang-Ming University, Taipei, 112, Taiwan; Department of Education and Research, Taipei City Hospital, Taipei, 112, Taiwan. Electronic address: khsun@ym.edu.tw.
authors.forename: Kuang-Hui
authors.initials: KH
authors.lastname: Sun
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D053264:B-Cell Activating Factor / Q000096:biosynthesis*; D002648:Child; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005786:Gene Expression Regulation; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D009154:Mutation; D009928:Organ Specificity; D012720:Severity of Illness Index; D000073871:Triggering Receptor Expressed on Myeloid Cells-1 / Q000097:blood / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D053264:B-Cell Activating Factor; C505719:TNFSF13B protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
keywords: B cell-activating factor; Systemic lupus erythematosus; Triggering receptor expressed on myeloid cells-1; lpr mice