Tyrosine kinases of the Janus kinase family initiate cellular responses through their association with receptors for alpha-helical cytokines. In addition to a tyrosine kinase domain, these enzymes possess a kinase-like (KL) domain, whose function remains elusive. To investigate the role of the KL domain of Tyk2 in interferon-alpha/beta signaling, we transfected a library of Tyk2 cDNAs containin...

In a 1984 review, Shlomo Eisenberg1 wrote, “In spite of their large number in plasma, it is difficult to define HDL as a vehicle for lipid transport ... other considerations must apply to this lipoprotein.” In this issue of Circulation, Suzuki et al2 report that high-density lipoprotein (HDL) suppresses the type I interferon response in macrophages challenged with lipopolysaccharide. They found...

The scavenger receptor type B class I(SR-BI) is a receptor for high-density lipoproteins(HDL) and one of entry factors for hepatitis C virus(HCV). We examined the association of single nucleotide polymorphisms(SNPs) of the SCARB1 gene, which encodes SR-BI, with virologic responses to pegylated interferon-based treatment in Asian chronic hepatitis C(CHC) patients. Human genomic and clinical data...

Hepatitis C virus (HCV) infection induces steatosis and is accompanied by multiple metabolic alterations including hyperuricemia, reversible hypocholesterolemia and insulin resistance. Total cholesterol, low-density lipoprotein-cholesterol and triglyceride levels are increased by peginterferon and ribavirin combination therapy when a sustained virologic response (SVR) is achieved in patients wi...

STAT3 is an oncogenic transcription factor with potent immunosuppressive functions. We found that pharmacologic inhibitionof STAT3or its selective knockout in cancer cells improved the tumor growth-inhibitory efficacy of anthracycline-based chemotherapies. This combined effect of STAT3 inhibition/depletion and anthracyclines was only found in tumors growing on immunocompetent (not in immunodefi...

Interleukin 17 (IL-17) and its receptor IL-17R1 produced by T-helper cells named Th17 are involved in the pathology of autoimmune diseases. In contrast to the at least partially explained role of IL-17 in pathology of multiple sclerosis, the significance of IL-17R in MS is unclear. Therefore we have studied the expression of IL-17R in the stable phase of multiple sclerosis treated by interferon...

The propensity of RNA viruses to revert attenuating mutations contributes to disease and complicates vaccine development. Despite the presence of virulent revertant viruses in some live-attenuated vaccines, disease from vaccination is rare. This suggests that in mixed viral populations, attenuated viruses may limit the pathogenesis of virulent viruses, thus establishing a virulence threshold. H...

The non-receptor tyrosine kinase TYK2 is a key component of the interferon signalling pathway. It can bind to the interferon ·/ß receptor where it mediates, together with another nonreceptor tyrosine kinase called JAK1, the phosphorylation of downstream targets. Other cytokine receptors that mediate their signals via TYK2 include the receptors for IL-6, IL-11, CNTF, LIF, and oncostatin M (Brisc...

Abstract The intestinal microbiota contributes to gut immune homeostasis, where short-chain fatty acids (SCFAs) function as the major mediators. We aimed elucidate immunomodulatory effects of acetate, propionate, and butyrate. With that in mind, we sought characterise expression SCFA receptors transporters well SCFAs’ impact on activation different cells. Whereas all three SCFAs decreased tumou...

Detection of the mouse hepatitis virus receptor within the central nervous system (CNS) has been elusive. Receptor expression on microglia was reduced during acute infection and restored following immune-mediated virus control. Receptor down regulation was independent of neutrophils, NK cells, gamma interferon, or perforin. Infection of mice devoid of distinct inflammatory cells revealed CD4(+)...