The STAT transcription factor STAT4 is a critical regulator of Th1 differentiation and inflammatory disease. Yet, how STAT4 regulates gene expression is still unclear. In this report, we define a STAT4-dependent sequence of events including histone H3 lysine 4 methylation, Jmjd3 association with STAT4 target loci, and a Jmjd3-dependent decrease in histone H3 lysine 27 trimethylation and DNA met...

INTRODUCTION STAT4 (signal transducer and activator of transcription 4) is involved in the regulation of innate and adaptive immune responses. Some studies have suggested that STAT4 may be involved in the immune response after graft transplantation. Several polymorphisms in the STAT4 gene have been identified. The most commonly studied polymorphism in the STAT4 gene is rs7574865. In our study, ...

We examined the immunological abnormality in a patient with recurrent Mycobacterium avium infection. T cells from the patient showed decreased ability both to produce IFN-gamma and to proliferate in response to IL-12. Despite decreased expression of IL-12R beta1 and beta2 chains in the patient's PHA-activated T cells, there was no difference in IL-12-induced tyrosine and serine phosphorylation ...

Autocrine activation of APC by IL-12 has recently been revealed; we demonstrate here that inducible expression of Stat4 in APC is central to this process. Stat4 is induced in dendritic cells (DC) in a maturation-dependent manner and in macrophages in an activation-dependent manner. Stat4 levels directly correlate with IL-12-dependent IFN-gamma production by APC as well as IFN-gamma production b...

Signal transducer and activator of transcription 4 (STAT4), a STAT family member, mediates interleukin 12 (IL12) signal transduction. IL12 is known to be related to calorie-restricted status. In the central nervous system, IL12 also enhances the production of nitric oxide (NO), which regulates food intake. In this study, the expression of neuronal NO synthase (Nos1), which is also related to fo...

To determine the role of STAT4-dependent Th1 responses in the regulation of immunity to the helminth parasite Taenia crassiceps, we monitored infections with this parasite in resistant mice lacking the STAT4 gene. While T. crassiceps-infected STAT4(+/+) mice rapidly resolved the infection, STAT4(-/-) mice were highly susceptible to infection and displayed large parasite loads. Moreover, the ina...

Th17 play a central role in autoimmune inflammatory responses. Th1 are also necessary for autoimmune disease development. The interplay of Th1 signals and how they coordinate with Th17 during inflammatory disease pathogenesis are incompletely understood. In this study, by adding Stat4 deficiency to Stat6/T-bet double knockout, we further dissected the role of Stat4 in Th1 development and coliti...

IL-12 activates STAT4, which is a critical regulator of inflammation and T helper type I (Th1) lineage development in murine systems. The requirement for STAT4 in the generation of human Th1 cells has not been examined thoroughly. Compared with control Th1 cultures, expression of the Th1 genes IFNgamma, IL-12Rbeta2, and TNFalpha is greatly reduced in Th1 cultures of CD4 T cells isolated from ly...

Lupov, Ivan M.S., Purdue University, May 2011. Acquired STAT4 deficiency as a consequence of cancer chemotherapy. Major Professor: Hua-Chen Chang. Signal Transducer and Activator of Transcription 4 (STAT4) is an important transcription factor activated by IL-12 signaling. Activated STAT4 is essential for Th1 cell differentiation, a process characterized by increased potential for interferon (IF...

Abstract Signal transducer and activator of transcription 4 (STAT4) is a critical regulator inflammation in autoimmunity by acting as messenger for pro-inflammatory cytokines including IL-12 IL-23. In experimental autoimmune encephalomyelitis (EAE), an animal model multiple sclerosis, germ-line deletion STAT4 mice results resistance to the development paralysis. Here, we examined cell-specific ...