Dysregulation of the granulocyte-macrophage colony stimulating factor receptor is one of the causes of defective expression of CD80 antigen in systemic lupus erythematosus

Abstract

CD80 and CD86, expressed on the antigen-presenting cells (APCs) provide costimulatory signals for T lymphocytes. Recently, defective expression of CD80 has been reported in systemic lupus erythematosus (SLE) although its mechanism is unclear. Here, expression of the B7 antigens induced by interferon-gamma, interleukin-4 or granulocyte-macrophage stimulating-factor (GM-CSF) along the differentiation process of APCs was investigated. In contrast to CD86, expression of CD80 on the CD14+ cells induced by GM-CSF was reduced in SLE. GM-CSF receptor (GM-CSFR) was down-regulated by GM-CSF or phorbol 12-myristate 13-acetate in both of the normal controls and SLE patients, while this change was more remarkable in the latter. In the presence of 1-(5-isoquinolinsulfonyl)-2-methylpiperazine, an inhibitor of protein kinase C, the PMA-induced down-regulation of GM-CSFR was reversed in the normal controls but not in SLE. These data suggest that dysregulation of the GM-CSFR might be associated with the defective expression of CD80, leading to dysfunction of the APCs in SLE.

IL-6 Produced by Dendritic Cells from Lupus-Prone Mice Inhibits CD4+CD25+ T Cell Regulatory Functions

“…The reduction in expression level of activation markers on TC DCs is overall similar to what has been described in lupus patients (25)(26)(27) and more recently in NZM2410, B6.TC parental strain (28). Some differences in relative CD40 and CD86 expression between B6.TC and NZM2410 may be due to the non-Sle loci.…”

“…The number of circulating plasmacytoid DCs (pDCs) is reduced in lupus patients (19,20), and the number of total DCs is increased in the lymphoid organs of lupus-prone mice (21)(22)(23)(24). Abnormal costimulatory profiles have also been reported in lupus patients (25)(26)(27) and in BWF 1 or NZM2410 mice (28). DC functions have also been implicated in the pathogenesis of lupus.…”

The mechanism of nasal tolerance in lupus prone mice is T-cell anergy induced by immature B cells that lack B7 expression

“…B7/CD28 interactions may also contribute to disease in humans, although the exact role(s) of these molecules is still unclear. However, evidence supporting our hypothesis comes from the finding that expression of CD80 on APCs of SLE patients is intrinsically defective [33]. It has been previously reported that induction of nasal tolerance in lupus prone SNF1 mice resulted in the suppression of T-cell proliferative response, autoantibody production and disease progression [15].…”

Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus

“…Recent studies of interferon activity and lupus have suggested that interferon-stimulated genes, such as AIM2, participate in the development of SLE (Choubey and Panchanathan 2008). Dysregulation of colonystimulating factor 3 receptor (CSF3R) had previously been implicated in the defective expression of CD80 and the subsequent dysfunction of the antigen-presenting cells in SLE (Funauchi et al 2002). Matrix metalloproteinases, such as MMP14, contribute to tissue destruction, regeneration, inflammation, and apoptosis, and several of them are up-regulated by a range of injuries in the skin and are thought to be involved in some of the organ manifestations of SLE.…”