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Role of nucleic acid-sensing TLRs in diverse autoantibody specificities and anti-nuclear antibody-producing B cells

Academic Article
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Overview

authors

  • Koh, Y. T.
  • Scatizzi, J. C.
  • Gahan, J. D.
  • Lawson, Brian
  • BaccalĂ , Roberto
  • Pollard, Kenneth Michael
  • Beutler, Bruce
  • Theofilopoulos, Argyrios
  • Kono, Dwight

publication date

  • 2013

journal

  • Journal of Immunology  Journal

abstract

  • Nucleic acid (NA)-sensing TLRs (NA-TLRs) promote the induction of anti-nuclear Abs in systemic lupus erythematosus. However, the extent to which other nonnuclear pathogenic autoantibody specificities that occur in lupus and independently in other autoimmune diseases depend on NA-TLRs, and which immune cells require NA-TLRs in systemic autoimmunity, remains to be determined. Using Unc93b1(3d) lupus-prone mice that lack NA-TLR signaling, we found that all pathogenic nonnuclear autoantibody specificities examined, even anti-RBC, required NA-TLRs. Furthermore, we document that NA-TLRs in B cells were required for the development of antichromatin and rheumatoid factor. These findings support a unifying NA-TLR-mediated mechanism of autoantibody production that has both pathophysiological and therapeutic implications for systemic lupus erythematosus and several other humoral-mediated autoimmune diseases. In particular, our findings suggest that targeting of NA-TLR signaling in B cells alone would be sufficient to specifically block production of a broad diversity of autoantibodies.

subject areas

  • Animals
  • Antibodies, Antinuclear
  • Antibody-Producing Cells
  • Autoantibodies
  • B-Lymphocytes
  • Bone Marrow Cells
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Chromatin
  • Dendritic Cells
  • Female
  • Immunologic Deficiency Syndromes
  • Lupus Erythematosus, Systemic
  • Lymphocyte Activation
  • Macrophages
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Mice
  • Mice, Inbred NZB
  • Myeloid Differentiation Factor 88
  • Nucleic Acids
  • Rheumatoid Factor
  • Ribonucleoproteins
  • Signal Transduction
  • Toll-Like Receptor 7
  • Toll-Like Receptor 9
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Identity

PubMed Central ID

  • PMC3729324

International Standard Serial Number (ISSN)

  • 1550-6606 (Electronic) 0022-1767 (Linking)

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.1202986

PubMed ID

  • 23589617
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Additional Document Info

start page

  • 4982

end page

  • 4990

volume

  • 190

issue

  • 10

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