Tpl2 (Tumor progression locus 2), also known as Cot/MAP3K8, is a hematopoietically expressed serine-threonine kinase. Tpl2 is known to have critical functions in innate immunity in regulating tumor necrosis factor-alpha, Toll-like receptor, and G protein-coupled receptor signaling; however, our understanding of its physiological role in T cells is limited. We investigated the potential roles of...

The immune system is an important target for the cytokine TGF-beta1, whose actions on lymphocytes are largely inhibitory. TGF-beta has been reported to inhibit IL-12- and IL-2-induced cell proliferation and IFN-gamma production by T cells and NK cells; however, the mechanisms of inhibition have not been clearly defined. It has been suggested by some studies that TGF-beta blocks cytokine-induced...

PURPOSE Cytokines, hormones and growth factors use signal transducers and activators of transcription (STAT) signaling pathways to control various biological responses, including development, differentiation, cell proliferation and survival. Constitutive activation of STATs has been found in a wide variety of human tumors. In this study we examined the activity of STATs in primary human prostat...

Rheumatoid arthritis is inherited in a complex manner. So far several single susceptibility genes, such as PTPN22, STAT4, and TRAF1-C5, have been identified. However, it is presumed that some genes may interact to have a significant effect on the disease, while each of them only plays a modest role. We propose a new combinatorial association test to detect the gene-gene interaction in the rheum...

BACKGROUND: Allergic subjects produce relatively low amounts of IFN-gamma, a pleiotropic Th-1 cytokine that downregulates Th2-associated airway inflammation and hyperresponsiveness (AHR), the hallmarks of allergic asthma. Adenovirus-mediated IFN-gamma gene transfer reduces AHR, Th2 cytokine levels and lung inflammation in mice, but its use would be limited by the frequency of gene delivery requ...

Expression of high affinity IL-12 receptors is required for IL-12-mediated IFN-gamma production. Activation of this pathway has been shown to be critical in generating optimal cell-mediated immunity. Therefore, increased IL-12 receptor expression might be expected in the host response after infection by an intracellular bacterial pathogen. In the present study, we have made the surprising disco...

IL-17-secreting CD4(+) T cells are critically involved in inflammatory immune responses. Development of these cells is promoted in vivo and in vitro by IL-23 or TGFbeta1 plus IL-6. Despite growing interest in this inflammatory Th subset, little is known about the transcription factors that are required for their development. We demonstrate that Stat3 is required for programming the TGFbeta1 plu...

Hepatitis B virus (HBV) infection is the leading cause of hepatocellular carcinoma (HCC) development. Recent studies demonstrated that single nucleotide polymorphisms (SNPs) rs2293152 in signal transducer and activator of transcription 3 (STAT3) and rs7574865 in signal transducer and activator of transcription 4 (STAT4) are associated with chronic hepatitis B (CHB)-related HCC in the Chinese po...

Previously, a dominant role of the adaptive immune system in the pathogenesis of Sjögren's syndrome was suspected. Recent advances, however, have revealed a major role of the type I IFN pathway, documented by an increased circulating type I IFN activity and an IFN 'signature' in peripheral blood mononuclear cells and minor salivary gland biopsies from the patients. Polymorphisms in the genes IR...