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.
Highlights
Renal inflammation leading to organ dysfunction and end-stage disease is a common feature of autoimmune diseases such as systemic lupus erythematosus (SLE) [1, 2]
We examined the ratio of Triggering Receptor of Myeloid Cells-1 (TREM-1) to TREM-2 messenger RNA (mRNA) expression by macrophages in anti-GBM-diseased kidneys on day 7 by Illumina arrays
Soluble TREM-1 was elevated in the serum of 129/SvJ compared to control B6 mice at later timepoints, this was correlated with a slight decrease in B6 serum soluble TREM-1 levels at days 14 and 21 in response to anti-GBM treatment (Fig. 1c)
Summary
Renal inflammation leading to organ dysfunction and end-stage disease is a common feature of autoimmune diseases such as systemic lupus erythematosus (SLE) [1, 2]. Davis and Chandra Mohan are co-senior authors. 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 Resident macrophages and recruited monocytes regulate renal inflammation which can involve renal cells [8, 9]
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