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. 2009 Nov;128(3):334-41.
doi: 10.1111/j.1365-2567.2009.03138.x.

Disease activity in systemic lupus erythematosus is associated with an altered expression of low-affinity Fc gamma receptors and costimulatory molecules on dendritic cells

Leandro J Carreño  1 , Rodrigo Pacheco, Miguel A Gutierrez, Sergio Jacobelli, Alexis M Kalergis
Affiliations

Disease activity in systemic lupus erythematosus is associated with an altered expression of low-affinity Fc gamma receptors and costimulatory molecules on dendritic cells

Leandro J Carreño et al. Immunology. 2009 Nov.

Abstract

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.

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Figures

Figure 1
Figure 1
Dendritic cells derived from patients with systemic lupus erythematosus (SLE) have an altered expression of costimulatory molecules on their surface. Immature dendritic cells (iDCs) or dendritic cells matured with 5 μg/ml of lipopolysaccharide (LPS) (mDCs) obtained from SLE patients or from healthy donors were labelled with specific conjugated monoclonal antibodies directed against CD11c and CD40, CD83, CD86 or CD80 and analyzed using flow cytometry. The mean fluorescence intensity (MFI) of human leucocyte antigen (HLA)-DR+ CD11c+ cells from 20 healthy donors and from 31 SLE patients were plotted for CD40 (a), CD86 (b), CD80 (c) and CD83 (d) expression. White bars represent healthy donors (Control) and black bars represent SLE patients (SLE). Data represent mean ± standard error of the mean (SEM). *P < 0·05; **P < 0·01.
Figure 2
Figure 2
The ratio of CD86/CD80 expression is abnormally high on dendritic cells (DCs) from patients with systemic lupus erythematosus (SLE). The ratio of CD86/CD80 expression was analyzed on immature and mature DCs from SLE patients and from healthy donors. The bars show the ratios of CD86 : CD80 expression, calculated from the data presented in Fig. 1b,c. White bars represent healthy donors and black bars represent SLE patients. The results represent the mean ± standard error of the mean (SEM). *P < 0·05; **P < 0·01.
Figure 3
Figure 3
Fcγ receptors (FcγRs) on dendritic cells (DCs) from patients with systemic lupus erythematosus (SLE) present an expression pattern skewed towards an overactivated DC phenotype. Expression of the activating receptor CD32a (a) and of the inhibitory receptor CD32b (b) were analyzed on immature DCs (iDCs) or on DCs matured with 5 μg/ml of lipopolysaccharide (LPS) (mDCs) obtained from SLE patients or from healthy donors. Graphs represent the mean fluorescence intensity for each antibody staining (c) The ratio of expression between CD32a and CD32b was plotted for iDCs and mDCs, for SLE patients and healthy donors. White bars represent healthy donors (Control) and black bars represent SLE patients (SLE). The results show the mean ± standard error of the mean (SEM). *P < 0·05; **P < 0·01.
Figure 4
Figure 4
Alterations in the ratio of activating/inhibitory Fcγ receptors (FcγRs) correlate with the severity of systemic lupus erythematosus (SLE). The SLE Disease Activity Index (SLEDAI) was plotted for each of 20 patients against each respective CD32a/CD32b ratio for immature dendritic cells (iDCs) and for mature dendritic cells (mDCs). Statistical analysis shows a Spearman r value of 0·44 for iDCs, and a Spearman r value of 0·71 for iDCs (P values of 0·06 and 0·0006, respectively).
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References

    1. Gonzalez PA, Carreno LJ, Figueroa CA, Kalergis AM. Modulation of immunological synapse by membrane-bound and soluble ligands. Cytokine Growth Factor Rev. 2007;18:19–31. - PubMed
    1. Iruretagoyena MI, Wiesendanger M, Kalergis AM. The dendritic cell-T cell synapse as a determinant of autoimmune pathogenesis. Curr Pharm Des. 2006;12:131–47. - PubMed
    1. Kalergis AM. Modulation of T cell immunity by TCR/pMHC dwell time and activating/inhibitory receptor pairs on the antigen-presenting cell. Curr Pharm Des. 2003;9:233–44. - PubMed
    1. Lipscomb MF, Masten BJ. Dendritic cells: immune regulators in health and disease. Physiol Rev. 2002;82:97–130. - PubMed
    1. Janeway CA., Jr How the immune system works to protect the host from infection: a personal view. Proc Natl Acad Sci USA. 2001;98:7461–8. - PMC - PubMed

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