Interferon

About: Interferon is a research topic. Over the lifetime, 28969 publications have been published within this topic receiving 1219645 citations. The topic is also known as: IFN & interferons.

Recombinant interleukin-2 directly augments the cytotoxicity of human monocytes.

Abstract: Interleukin-2 (IL-2), originally described as a growth factor required for sustained proliferation of T cells in vitro1,2 is a glycoprotein hormone of known structure3 which appears to be important for the generation of immune responses in vivo4. As well as T lymphocytes, B lymphocytes5 and large granular lymphocytes with natural killer activity (NK cells)6 can also respond to IL-2. The action of IL-2 seemed to be limited specifically to lymphocytes, however, and the term 'T-lymphocytotrophic hormone' was used7. Here we provide evidence that human monocytes display a substantially increased cytotoxic activity as a direct and rapid response to human recombinant IL-2 but not to human recombinant glycosylated interferon-γ (IFN-γ) or lipopolysac-charide. Our results reveal a previously unknown function of IL-2 and suggest its possible involvement in monocyte-T cell interactions.

Toll-Like Receptor Engagement Enhances the Immunosuppressive Properties of Human Bone Marrow-Derived Mesenchymal Stem Cells by Inducing Indoleamine-2,3-dioxygenase-1 via Interferon-β and Protein Kinase R

Abstract: Mesenchymal stem cells (MSC) display unique suppressive properties on T-cell immunity, thus representing an attractive vehicle for the treatment of conditions associated with harmful T-cell responses such as organ-specific autoimmunity and graft-versus-host disease. Toll-like receptors (TLR) are primarily expressed on antigen-presenting cells and recognize conserved pathogen-derived components. Ligation of TLR activates multiple innate and adaptive immune response pathways to eliminate and protect against invading pathogens. In this work, we show that TLR expressed on human bone marrow-derived MSC enhanced the immunosuppressive phenotype of MSC. Immunosuppression mediated by TLR was dependent on the production of immunosuppressive kynurenines by the tryptophan-degrading enzyme indoleamine-2,3-dioxygenase-1 (IDO1). Induction of IDO1 by TLR involved an autocrine interferon (IFN)-beta signaling loop, which was dependent on protein kinase R (PKR), but independent of IFN-gamma. These data define a new role for TLR in MSC immunobiology, which is to augment the immunosuppressive properties of MSC in the absence of IFN-gamma rather than inducing proinflammatory immune response pathways. PKR and IFN-beta play a central, previously unidentified role in orchestrating the production of immunosuppressive kynurenines by MSC.

A macrophage marker, Siglec-1, is increased on circulating monocytes in patients with systemic sclerosis and induced by type I interferons and toll-like receptor agonists.

Abstract: Objective Microarray analyses of peripheral blood leukocytes have shown that patients with systemic lupus erythematosus express increased levels of type I interferon (IFN)–regulated genes. In this study we examined gene expression by peripheral blood mononuclear cells (PBMCs) from patients with systemic sclerosis (SSc) to better understand the dysregulation of the immune system in this disease. Methods PBMC gene expression was analyzed by microarray and confirmed by real-time polymerase chain reaction (PCR). Surface protein expression of Siglec-1 was analyzed by flow cytometry in PBMCs from healthy control subjects and patients with SSc, and in control PBMCs that were cultured in vitro with Toll-like receptor (TLR) agonists. Results SSc patients showed increased expression of a cluster of IFN-regulated genes, including Siglec-1 (CD169, sialoadhesin). This result was verified and extended by real-time PCR, showing that a subset of the SSc patients expressed strikingly increased levels of Siglec-1 messenger RNA (mRNA). Flow cytometry of PBMCs from SSc patients and healthy controls showed increased Siglec-1 surface protein expression, which was restricted to CD14+ monocytes. In vitro studies showed that type I IFN and certain TLR agonists, including TLR-7 and TLR-9, induced Siglec-1 mRNA and protein expression. Moreover, TLR induction of surface Siglec-1 was shown to be type I IFN–dependent. Increased numbers of Siglec-1+ cells were observed by immunohistochemistry in the skin of SSc patients compared with healthy controls. Conclusion Increased expression of Siglec-1 in circulating SSc monocytes and tissue macrophages suggests that type I IFN–mediated activation of monocytes occurs in SSc, possibly through TLR activation of IFN secretion. These observations indicate a potential role for type I IFN–activated monocyte/macrophages in the pathogenesis of SSc.