FcR-bearing myeloid cells are responsible for triggering murine lupus nephritis

Amy Bergtold, Anamika Gavhane, Vivette D'Agati, Michael Madaio, Raphael Clynes

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79 Scopus citations

Abstract

Lupus glomerulonephritis is initiated by deposition of IgG-containing immune complexes in renal glomeruli. FcR engagement by immune complexes (IC) is crucial to disease development as uncoupling this pathway in FcRγ-/- abrogates inflammatory responses in (NZB × NZW)F1 mice. To define the roles of FcR-bearing hemopoietic cells and of kidney resident mesangial cells in pathogenesis, (NZB × NZW)F 1 bone marrow chimeras were generated. Nephritis developed in (NZB × NZW)F1 mice expressing activating FcRs in hemopoietic cells. Conversely, recipients of FcRγ-/- bone marrow were protected from disease development despite persistent expression of FcRγ in mesangial cell populations. Thus, activating FcRs on circulating hemopoietic cells, rather than on mesangial cells, are required for IC-mediated pathogenesis in (NZB × NZW)F1. Transgenic FcRγ-/- mice expressing FcRγ limited to the CD11b+ monocyte/macrophage compartment developed glomerulonephritis in the anti-glomerular basement disease model, whereas nontransgenic FcRγ-/- mice were completely protected. Thus, direct activation of circulating FcR-bearing myeloid cells, including monocytes/macrophages, by glomerular IC deposits is sufficient to initiate inflammatory responses.

Original languageEnglish (US)
Pages (from-to)7287-7295
Number of pages9
JournalJournal of Immunology
Volume177
Issue number10
DOIs
Publication statusPublished - Nov 15 2006

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Bergtold, A., Gavhane, A., D'Agati, V., Madaio, M., & Clynes, R. (2006). FcR-bearing myeloid cells are responsible for triggering murine lupus nephritis. Journal of Immunology, 177(10), 7287-7295. https://doi.org/10.4049/jimmunol.177.10.7287