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.

Immune interferon in the circulation of patients with autoimmune disease.

Abstract: The observation that type II, or immune, interferon could be produced by peripheral-blood leukocytes in vitro on an immune-specific basis suggested that it also might be produced in vivo in various autoimmune disorders. We found immune interferon in the serums of patients with systemic lupus erythematosus, rheumatoid arthritis, scleroderma and Sjogren's syndrome. Among 28 patients with systemic lupus erythematosus, 71 per cent of those with active and 21 per cent of those with inactive disease showed interferon in their serums. Serial serum samples showed a good correlation between interferon titers and disease activity. Moreover, interferon titers correlated positively with antibodies to DNA and negatively with serum levels of the third component of complement. It is possible that the production of interferon may contribute to immunologic aberrations in auto-immune diseases and also protect the already compromised host from viral infections.

PKR; a sentinel kinase for cellular stress.

Abstract: The double stranded RNA (dsRNA)-activated protein kinase PKR is a ubiquitously expressed serine/threonine protein kinase that is induced by interferon and activated by dsRNA, cytokine, growth factor and stress signals. It is essential for cells to respond adequately to different stresses including growth factor deprivation, products of the inflammatory response (TNF) and bacterial (lipopolysaccharide) and viral (dsRNA) products. As a vital component of the cellular antiviral response pathway, PKR is autophosphorylated and activated on binding to dsRNA. This results in inhibition of protein synthesis via the phosphorylation of eIF2alpha and also induces transcription of inflammatory genes by PKR-dependent signaling of the activation of different transcription factors. Along with RNaseL, PKR constitutes the antiviral arm of a group of mammalian stress response proteins that have counterparts in yeast. What began as adaptation to amino acid deprivation and sensing unfolded proteins in the endoplasmic reticulum has evolved into a family of sophisticated mammalian stress response proteins able to mediate cellular responses to both physical and biological stress.

Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model

Abstract: This report shows that interleukin (IL) 17–producing T helper type 17 (Th17) cells predominantly express CC chemokine receptor (CCR) 6 in an animal model of rheumatoid arthritis (RA). Th17 cells induced in vivo in normal mice via homeostatic proliferation similarly express CCR6, whereas those inducible in vitro by transforming growth factor β and IL-6 additionally need IL-1 and neutralization of interferon (IFN) γ and IL-4 for CCR6 expression. Forced expression of RORγt, a key transcription factor for Th17 cell differentiation, induces not only IL-17 but also CCR6 in naive T cells. Furthermore, Th17 cells produce CCL20, the known ligand for CCR6. Synoviocytes from arthritic joints of mice and humans also produce a large amount of CCL20, with a significant correlation (P = 0.014) between the amounts of IL-17 and CCL20 in RA joints. The CCL20 production by synoviocytes is augmented in vitro by IL-1β, IL-17, or tumor necrosis factor α, and is suppressed by IFN-γ or IL-4. Administration of blocking anti-CCR6 monoclonal antibody substantially inhibits mouse arthritis. Thus, the joint cytokine milieu formed by T cells and synovial cells controls the production of CCL20 and, consequently, the recruitment of CCR6+ arthritogenic Th17 cells to the inflamed joints. These results indicate that CCR6 expression contributes to Th17 cell function in autoimmune disease, especially in autoimmune arthritis such as RA.

Human type 1 innate lymphoid cells accumulate in inflamed mucosal tissues

Abstract: Innate lymphoid cells (ILCs) are effectors of innate immunity and regulators of tissue modeling Recently identified ILC populations have a cytokine expression pattern that resembles that of the helper T cell subsets T(H)2, T(H)17 and T(H)22 Here we describe a distinct ILC subset similar to T(H)1 cells, which we call 'ILC1' ILC1 cells expressed the transcription factor T-bet and responded to interleukin 12 (IL-12) by producing interferon-γ (IFN-γ) ILC1 cells were distinct from natural killer (NK) cells as they lacked perforin, granzyme B and the NK cell markers CD56, CD16 and CD94, and could develop from RORγt(+) ILC3 under the influence of IL-12 The frequency of the ILC1 subset was much higher in inflamed intestine of people with Crohn's disease, which indicated a role for these IFN-γ-producing ILC1 cells in the pathogenesis of gut mucosal inflammation

Requirement for transcription factor IRF-1 in NO synthase induction in macrophages.

Abstract: Production of nitric oxide (NO) by macrophages is important for the killing of intracellular infectious agents Interferon (IFN)-gamma and lipopolysaccharide stimulate NO production by transcriptionally up-regulating the inducible NO synthase (iNOS) Macrophages from mice with a targeted disruption of the IFN regulatory factor-1 (IRF-1) gene (IRF-1-/- mice) produced little or no NO and synthesized barely detectable iNOS messenger RNA in response to stimulation Two adjacent IRF-1 response elements were identified in the iNOS promoter Infection with Mycobacterium bovis (BCG) was more severe in IRF-1-/- mice than in wild-type mice Thus, IRF-1 is essential for iNOS activation in murine macrophages