IFN-γ licenses CD11b(+) cells to induce progression of systemic lupus erythematosus

J Autoimmun. 2015 Aug:62:11-21. doi: 10.1016/j.jaut.2015.05.007. Epub 2015 Jun 19.

Abstract

Autoantibodies are a hallmark of autoimmune diseases, such as rheumatoid arthritis, autoimmune hepatitis, and systemic lupus erythematosus (SLE). High titers of anti-nuclear antibodies are used as surrogate marker for SLE, however their contribution to pathogenesis remains unclear. Using murine model of SLE and human samples, we studied the effect of immune stimulation on relapsing of SLE. Although autoantibodies bound to target cells in vivo, only additional activation of CD8(+) T cells converted this silent autoimmunity into overt disease. In mice as well as in humans CD8(+) T cells derived IFN-γ enhanced expression of Fc-receptors on CD11b(+) cells. High expression of Fc-receptors allowed CD11b(+) cells to bind to antibody covered target cells and to destroy them in vivo. We found that autoantibodies induce clinically relevant disease when adaptive immunity, specific for disease non-related antigen, is activated.

Keywords: Autoantibodies; Fcgr2b; IFN-γ; Infection; Inflammation; Systemic lupus erythematosus; Virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / immunology
  • Autoimmunity / immunology
  • CD11b Antigen / metabolism*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Disease Models, Animal
  • Disease Progression
  • Humans
  • Interferon-gamma / metabolism*
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / metabolism*
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Lymphocyte Count
  • Lymphocyte Subsets / immunology*
  • Lymphocyte Subsets / metabolism*
  • Mice
  • Mice, Knockout
  • Receptors, IgG / genetics
  • Recurrence

Substances

  • Autoantibodies
  • CD11b Antigen
  • Receptors, IgG
  • Interferon-gamma