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Glomerulonephritis is a common and debilitating feature of systemic lupus erythematosus (SLE). The precise immune mechanisms that drive the progression from benign autoimmunity to glomerulonephritis are largely unknown. Previous investigations have shown that a moderate increase of the innate Toll-like receptor 7 (TLR7) is sufficient for the development of nephritis. In these systems normalization of B-cell TLR7 expression or temporal depletion of plasmacytoid dendritic cells (pDCs) slow progression; however, the critical cell that is responsible for driving full immunopathology remains unidentified. In this investigation we have shown that conventional DC expression of TLR7 is essential for severe autoimmunity in the Sle1Tg7 model of SLE. We show that a novel expanding CD11b(+) conventional DC subpopulation dominates the infiltrating renal inflammatory milieu, localizing to the glomeruli. Moreover, exposure of human myeloid DCs to IFN-α or Flu increases TLR7 expression, suggesting they may have a role in self-RNA recognition pathways in clinical disease. To our knowledge, this study is the first to highlight the importance of conventional DC-TLR7 expression for kidney pathogenesis in a murine model of SLE.

Original publication





Proceedings of the National Academy of Sciences of the United States of America

Publication Date





E6195 - E6204


Singapore Immunology Network, A*STAR, 138648 Singapore;


Kidney Glomerulus, Dendritic Cells, Animals, Humans, Mice, Lupus Nephritis, DNA Primers, Microscopy, Confocal, Flow Cytometry, Analysis of Variance, Statistics, Nonparametric, Gene Expression Profiling, Sequence Analysis, RNA, Up-Regulation, Base Sequence, Image Processing, Computer-Assisted, Molecular Sequence Data, Toll-Like Receptor 7, Real-Time Polymerase Chain Reaction, CD11b Antigen