Disease activity in systemic lupus erythematosus is associated with an altered expression of low-affinity Fc gamma receptors and costimulatory molecules on dendritic cells.
Dendritic cells (DCs) play a pivotal role in the interface between immunity and maintenance of peripheral tolerance. The capture of immunoglobulin G (IgG)-containing immune complexes (ICs) by low-affinity Fc gamma receptors (Fc gammaRs) expressed on DCs may influence the immunogenicity/tolerogenicity of these cells, depending on the activating/inhibitory potential of Fc gammaRs. Because of the key role that low-affinity Fc gammaRs play in determining the magnitude of the response in IC-driven inflammation, these receptors are likely to play a role in autoimmune diseases, such as systemic lupus erythematosus (SLE). To evaluate if an altered expression of costimulatory molecules and/or Fc gammaRs could account for disease severity, we evaluated the expression of these molecules on immature and mature DCs derived from peripheral blood monocytes of SLE patients and healthy donors. Our results show an increased expression of the costimulatory molecules CD40 and CD86. Furthermore, the ratio of CD86/CD80 is higher in SLE patients compared with healthy donors. Conversely, while the expression of activating Fc gammaRs was higher on DCs from SLE patients, expression of inhibitory Fc gammaRs was lower, compared with DCs obtained from healthy donors. As a result, the activating to inhibitory Fc gammaR ratio was significantly higher in DCs from SLE patients. The altered ratio of activating/inhibitory Fc gammaRs on mature DCs showed a significant correlation with the activity of SLE, as determined by the SLE Disease Activity Index (SLEDAI) score. We postulate that the increased ratio of activating/inhibitory Fc gammaRs expressed on DCs from SLE patients can contribute to the failure of peripheral tolerance in the IC-mediated phase of autoimmune pathogenesis.
Carreño
Leandro J
LJ
Millennium Nucleus on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
Pacheco
Rodrigo
R
Gutierrez
Miguel A
MA
Jacobelli
Sergio
S
Kalergis
Alexis M
AM
D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D056747:Immunomodulation; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D017452:Receptors, IgG / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D017634:Self Tolerance; D012720:Severity of Illness Index
D015703:Antigens, CD; D017452:Receptors, IgG