Defective expression and function of the ILT2/CD85j regulatory receptor in dendritic cells from patients with systemic lupus erythematosus.

Dendritic cells (DCs) play an important role in inducing immune tolerance. Inhibitory receptors, such as ILT2/CD85j, are involved in the tolerogenic effect of DCs and previous studies have indicated the important role of these receptors on the pathogenesis of autoimmune diseases. The aim of this study was to evaluate the expression and function of ILT2 in DCs from SLE patients. Peripheral blood from fifty patients with SLE and 38 healthy volunteers was obtained. ILT2 expression was assessed by flow cytometry. DCs were generated in the absence or presence of an anti-ILT2 antibody. The effect of ILT2 in the immunogenic ability of SLE DCs was also evaluated. We observed that SLE patients had significant higher levels of circulating plasmacytoid DCs (pDCs), and that these levels correlated with disease activity. In contrast, the expression of ILT2 was diminished in both pDCs and myeloid DCs (mDCs) from these patients. However, under our experimental conditions, the in vitro differentiation of DCs was not apparently affected by ILT2 engagement. In contrast, the immunogenic capability of monocyte-derived DCs was not down-regulated by ILT2 cross-linking in a significant proportion of SLE patients. Our results suggest that ILT2 participates in the defective immune-regulation observed in patients with SLE.

Plasmacytoid dendritic cells: key players in viral infections and autoimmune diseases.

OBJECTIVE: Describe the main activation and inhibitory pathways and receptors by which pDC regulate type I interferon secretion, as well as its association with autoimmune pathology. METHODS: A PubMed search for articles was conducted using the following key words: plasmacytoid dendritic cells, autoimmune diseases, viral infections and type I interferon. The search was limited to publications in English and from 1957 to 2012. Sixty-five of these articles are included in this review. The most relevant primary research articles identified were critically evaluated and compiled together. Particularly, areas of consensus and controversy were identified and analyzed. RESULTS: Plasmacytoid dendritic cells have been closely related to viral infections and autoimmune disease, mainly because of these immune cells are able to secrete large amounts of type I interferon. This function is linked with their expression of Toll-like receptors, specially TLR7 and TLR9, which are designed to sense nucleic acids in the early endosomes. Activated pDC can promote immunity and autoimmunity, however, the exact mechanisms by which pDC promote one vs. the other are not well understood. CONCLUSIONS: Plasmacytoid dendritic cells play a key role in both, immunity and autoimmunity. Current evidence suggests that the sustained overproduction of type-I interferon drives aberrant immune responses and the development of autoimmune pathology.

Interferon regulatory factors: beyond the antiviral response and their link to the development of autoimmune pathology.

Abnormal production of interferon type I has been widely related to multiple autoimmune diseases, particularly systemic lupus erythematosus (SLE). It has been considered the molecular signature characterized by the overexpression of type I Interferon related genes in SLE patients. Among these, are the interferon regulatory factors (IRF). These transcription factors have been involved in the innate immune response, mainly the one related to the defense against viral infections; the development of immune cells and carcinogenesis. The role of IRF in autoimmune pathology has been addressed in diverse murine models. However, evidence in humans is quite scant. This review will focus on the evidence that supports the role of IRF in the development or susceptibility to autoimmune diseases. Specific emphasis will be made over the role of IRF-5 and IRF-7, since evidence of its association to the development of pathology, particularly systemic lupus erythematosus is the strongest.