Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/81194
Title: RNA sensing by conventional dendritic cells is central to the development of lupus nephritis
Authors: Celhar, Teja
Hopkins, Richard
Thornhill, Susannah I.
De Magalhaes, Raquel
Hwang, Sun-Hee
Lee, Hui-Yin
Yasuga, Hiroko
Jones, Leigh A.
Casco, Jose
Lee, Bernett
Thamboo, Thomas P.
Zhou, Xin J.
Poidinger, Michael
Connolly, John E.
Wakeland, Edward K.
Fairhurst, Anna-Marie
Keywords: Dendritic cells
SLE
Autoimmunity
TLR7
Nephritis
Issue Date: 2015
Source: Celhar, T., Hopkins, R., Thornhill, S. I., De Magalhaes, R., Hwang, S.-H., Lee, H.-Y., et al. (2015). RNA sensing by conventional dendritic cells is central to the development of lupus nephritis. Proceedings of the National Academy of Sciences, 112(45), 6195-6204.
Series/Report no.: Proceedings of the National Academy of Sciences of the United States of America
Abstract: 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.
URI: https://hdl.handle.net/10356/81194
http://hdl.handle.net/10220/39173
DOI: 10.1073/pnas.1507052112
Rights: © 2015 The Authors (Published by National Academy of Sciences).
Fulltext Permission: none
Fulltext Availability: No Fulltext
Appears in Collections:SBS Journal Articles

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