TY - JOUR
T1 - Blockade of CD354 (TREM-1) Ameliorates Anti-GBM-Induced Nephritis
AU - du, Yong
AU - Wu, Tianfu
AU - Zhou, Xin J.
AU - Davis, Laurie S.
AU - Mohan, Chandra
N1 - Funding Information:
All authors approved the article for submission and all authors were involved in drafting and/or revising the article. YD oversaw all aspects of the studies including study conception and design and supervised daily tasks for the murine nephritis induction and treatment studies, ELISAs, immunohistochemistry, data interpretation, statistical analysis, and writing of the manuscript; TW carried out array assays, data interpretation, and statistical analysis and reviewed the manuscript; XJZ is an expert in kidney pathobiology and contributed to study design and data interpretation, carried out blinded assessment of kidney scores, and performed histopathological scans and scores; LSD assisted with study supervision, data analysis, data interpretation, statistical analysis, and writing of the manuscript; and CM developed the anti-GBM assay and supervised the study including study conception and study design, data analysis, interpretation of the data and of the statistical analysis, and writing of the manuscript. Laurie S. Davis and Chandra Mohan are co-senior authors. These studies were supported by National Institutes of Health (NIH) Grants R01 AR050812 (PI, Mohan), DK081872 (PI, Mohan), and P50-AR055503 (PI, Mohan). Dr. Davis and Dr. Mohan are also supported by the Alliance for Lupus Research.
Funding Information:
These studies were supported by National Institutes of Health (NIH) Grants R01 AR050812 (PI, Mohan), DK081872 (PI, Mohan), and P50-AR055503 (PI, Mohan). Dr. Davis and Dr. Mohan are also supported by the Alliance for Lupus Research.
Publisher Copyright:
© 2016, The Author(s).
PY - 2016/6/1
Y1 - 2016/6/1
N2 - 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.
AB - 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.
KW - SLE, systemic lupus erythematosus
KW - Triggering Receptor Expressed by Myeloid Cells-1 (TREM-1)
KW - anti-glomerular basement membrane antibody-induced nephritis
KW - immune-mediated nephritis
KW - immunotherapy
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U2 - 10.1007/s10753-016-0351-1
DO - 10.1007/s10753-016-0351-1
M3 - Article
C2 - 27083877
AN - SCOPUS:84963776358
SN - 0360-3997
VL - 39
SP - 1169
EP - 1176
JO - Inflammation
JF - Inflammation
IS - 3
ER -