Activation of the interferon-γ signaling pathway in systemic lupus erythematosus peripheral blood mononuclear cells




To investigate interferon-γ (IFNγ) signaling in peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE) by analyzing IFNγ receptor (IFNγR) expression, STAT-1 expression and phosphorylation, and the regulation of IFNγ-inducible genes.


Fluorocytometry was used to investigate expression of STAT-1, pSTAT-1, CD95, HLA–DR, class I major histocompatibility complex (MHC), IFNγ-inducible 10-kd protein (IP-10), monokine induced by IFNγ (Mig), and IFNγR in PBMCs from SLE patients and healthy individuals. STAT-1 phosphorylation was determined by fluorocytometry and Western blotting after stimulation with IFNα or IFNγ. Quantitative polymerase chain reaction was used to assess messenger RNA (mRNA) expression of the IFNγ-inducible genes IP-10 and Mig shortly after preparation or after stimulation with IFNγ in monocytes.


STAT-1 expression was increased in PBMCs from SLE patients and correlated significantly with disease activity and with the IFN-inducible expression of CD95 and HLA–DR. STAT-1 expression also showed a trend toward association with class I MHC expression. In addition, the expression of other IFNγ-inducible genes, such as IP-10 or Mig, was increased in SLE monocytes. While STAT-1 phosphorylation in SLE PBMCs and PBMCs from healthy individuals was similar after IFNα stimulation, incubation with IFNγ induced STAT-1 phosphorylation only in SLE lymphocytes. Moreover, SLE monocytes showed a considerably higher increase in pSTAT-1 expression upon IFNγ stimulation than monocytes from healthy individuals. Increased responsiveness of SLE monocytes to IFNγ was also confirmed on the mRNA level, where expression of the IFN-inducible, STAT-1–dependent genes IP-10 and Mig was more efficiently increased in SLE cells. However, IFNγR was similarly expressed on SLE lymphocytes and monocytes and those from healthy individuals.


In addition to supporting the role of IFNs in SLE immunopathogenesis in general, the findings of the present study support a role of IFNγ in this disease.