title: Blockade of CD354 (TREM-1) Ameliorates Anti-GBM-Induced Nephritis.
abstract: CD354, Triggering Receptor of Myeloid Cells-1 (TREM-1), is a potent amplifier of myeloid immune responses. Our goal was to determine the expression and function of TREM-1 in immune-mediated nephritis. An anti-glomerular basement membrane antibody (anti-GBM)-induced nephritis model was employed, where mice were sensitized with rabbit IgG followed by anti-GBM serum to induce disease. Anti-GBM-treated 129x1/svJ mice developed severe nephritis whereas C57BL/6 (B6) mice were resistant to disease. Anti-GBM disease resulted in elevated renal TREM-1 messenger RNA (mRNA) and protein levels and increased urine TREM-1 levels in 129x1/svJ. TREM-1 blockade with an inhibitory peptide, LP17, inhibited proteinuria and renal disease as measured by glomerulonephritis class, severity of tubulointerstitial disease, crescent formation, and inflammatory cell infiltrates. In sum, TREM-1 is upregulated in renal inflammation and plays a vital role in driving disease. Thus, TREM-1 blockade emerges as a potential therapeutic avenue for immune-mediated renal diseases such as lupus nephritis.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Bldg Y, Flr 8, Room 206 (Y8.206), Dallas, TX, 75390-8884, USA.|Department of Biomedical Engineering, University of Houston, 3605 Cullen Blvd, Room 2027, Houston, TX, 77204-5060, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Du
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Bldg Y, Flr 8, Room 206 (Y8.206), Dallas, TX, 75390-8884, USA.|Department of Biomedical Engineering, University of Houston, 3605 Cullen Blvd, Room 2027, Houston, TX, 77204-5060, USA.
authors.forename: Tianfu
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
authors.forename: Xin J
authors.initials: XJ
authors.lastname: Zhou
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Bldg Y, Flr 8, Room 206 (Y8.206), Dallas, TX, 75390-8884, USA. Laurie.Davis@UTSouthwestern.edu.
authors.forename: Laurie S
authors.initials: LS
authors.lastname: Davis
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Bldg Y, Flr 8, Room 206 (Y8.206), Dallas, TX, 75390-8884, USA.|Department of Biomedical Engineering, University of Houston, 3605 Cullen Blvd, Room 2027, Houston, TX, 77204-5060, USA.
authors.forename: Chandra
authors.initials: C
authors.lastname: Mohan
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000494:pharmacology; D004195:Disease Models, Animal; D008181:Lupus Nephritis / Q000139:chemically induced / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000037:antagonists & inhibitors* / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D011971:Receptors, Immunologic / Q000032:analysis* / Q000037:antagonists & inhibitors* / Q000235:genetics; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D015854:Up-Regulation
chemical_list: D001323:Autoantibodies; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; C517262:TREM1 protein, mouse; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; C051951:antiglomerular basement membrane antibody
keywords: SLE, systemic lupus erythematosus; Triggering Receptor Expressed by Myeloid Cells-1 (TREM-1); anti-glomerular basement membrane antibody-induced nephritis; immune-mediated nephritis; immunotherapy