Up-regulated expression of Ro52/tripartite motif-containing protein 21 (TRIM21), Ro60/TROVE domain family, member 2 (TROVE2) and lupus LA protein/Sjögren's syndrome antigen B (La/SSB) autoantigens has been described in the salivary gland epithelial cells (SGEC) of patients with Sjögren's syndrome (SS).
Recent reports describe variable expression of a number of regulatory microRNAs in lupus CD4+ T cells, some of which govern the expression of DNA methyltransferase 1.
Taken together, these findings demonstrate an intrinsic role for IRF5 in the response of monocytes to pristane and their recruitment to the primary site of inflammation that is thought to trigger lupus onset in this experimental model of SLE.
Our observations provide new insights about the MZ B cell translocation in lupus patients as well as the dichotomy of TLR9 and TLR7 signals in the pathogenesis of lupus.
CD40L expression on activated lupus monocytes within anti-CD3-stimulated, mononuclear cell cultures was also enhanced compared to control-derived monocytes.
The clinical relevance of these findings was verified in a study of 152 lupus patients, in which we showed that lupus nTreg dysfunction is not due to intrinsic defects but is rather induced by C3b stimulation of CD46 and IFN-α and that these immune components of inflammation are directly associated with active lupus.
Given that the expression of some of the p200-family proteins is differentially regulated by sex hormones and these proteins differentially regulate cytosolic DNA-induced production of type I IFN and proinflammatory cytokines (IL-1β and IL-18), the major known contributors of SLE-associated inflammation, we discuss the recent advancements in our understanding of the role of p200-family proteins in lupus susceptibility modification.
Compared with controls, the expression of IRF7 mRNA was significantly increased in patients with SLE and was positively correlated with both the serum level of IFN-α and lupus disease activity.
Persistent production of IFN-α, the most abundant subtype measured in these patients, is an important feature of the immunopathogenesis of lupus and has stimulated current efforts to develop and test therapeutics that either block IFN-I or its receptor directly or target components of the IFN-I pathway involved in induction of or response to IFN-I.
Given that the murine lupus susceptibility locus Nba2 includes the IFN-regulated genes Ifi202 (encoding for the p202 protein), Aim2 (encoding for the Aim2 protein), and Fcgr2b (encoding for the FcγRIIB receptor), we investigated whether the IRF5/Blimp-1 axis could regulate the expression of these genes.
Given that the murine lupus susceptibility locus Nba2 includes the IFN-regulated genes Ifi202 (encoding for the p202 protein), Aim2 (encoding for the Aim2 protein), and Fcgr2b (encoding for the FcγRIIB receptor), we investigated whether the IRF5/Blimp-1 axis could regulate the expression of these genes.
This suggests that demethylation of genes on the inactive X may predispose women to lupus, and this hypothesis is supported by a report that CD40LG, an immune gene encoded on the X chromosome, demethylates and is overexpressed in T cells from women but not men with lupus.
Interleukin-17Ars2275913, Interleukin-17F rs763780 and rs2397084 gene polymorphisms as possible risk factors in Juvenile lupus and lupus related nephritis.
Lupus monocytes clearly overexpressed CD40L comparing to healthy and disease-control monocytes, and, similarly to lupus T cells, displayed a prominent resistance to CsA inhibitory effects.
These results demonstrate that both TLR9 and TLR4 are required for 'full-blown' autoimmunity and organ injury in experimental lupus induced by pristane.