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A molecular association between the strong genetic systemic lupus erythematosus risk variant in STAT4, rs7574865[T], and an augmented responsiveness to IL-12, which results in increased IFN-gamma production in T cells.
we analyzed common variants located in genes of the IL12/STAT4 and IL10/STAT3 signaling pathways in patients with myasthenia gravis.
Genetic susceptibility to Hepatitis B Virus persistence, hepatic inflammation and fibrosis in Caucasians associates with STAT4 rs7574865 variant. Downstream effects on NK cell function through STAT4 phosphorylation-dependent IFN-gamma production likely contribute to these effects.
Study revealed that STAT4 is involved in M2 macrophages polarization and that mir-320a is a new modulator of M2 switch through down-regulation of STAT4. mir-320a can be transferred from polymorphonuclear leukocytes, isolated from subjects at high-risk to develop lung cancer, to macrophages inducing an M2 polarization and may be involved in lung cancer development.
STAT4 rs7574865 polymorphism is associated with rheumatoid arthritis
the G allele of rs11893432 was significantly associated with juvenile idiopathic arthritis risk in Han Chinese populations. SNPs at rs1018981 and rs10931481 were correlated with higher risk of poly-articular juvenile idiopathic arthritis.
study revealed an association between STAT4 gene rs7574865 SNP and risk of RA.
We confirmed the association of Sjogren's syndrome with the STAT4 and IL10 genes and we describe a novel association with HCP5.
No single nucleotide polymorphisms within STAT4 were associated with Mycobacterium tuberculosis (MTB) infection and pulmonary tuberculosis (PTB). This study demonstrated that STAT4 variants were not related to latent tuberculosis infection and PTB.
luciferase assay indicated that miR-141 directly targeted the 3'-UTR predictive sequence of STAT4
These data suggest autosomal dominant STAT4 deficiency as a novel inborn error of IL-12-dependent IFN-gamma immunity associated with susceptibility to paracoccidioidomycosis.
Allele A of the rs4853542 polymorphism in STAT4 is not associated with TB susceptibility, but rs4853542A allele decreased risk of TB in younger adults after Bonferroni correction.
STAT4 role in the Th1/Th2 cell mediated immune responses in leprosy.
Study provides evidence that polymorphisms of rs7574865, rs3024921, rs6752770, rs7601754 and rs10168266 in STAT4 were significantly associated with the risk of primary biliary cholangitis.
Single nucleotide polymorphisms in ITGAM, TNFSF4, TNFAIP3 and STAT4 genes are associated with susceptibility to systemic lupus erythematosus in a North Indian population.
the present study postulates that the genetic variation of the transcription factor GATA3, not STAT4, is associated with the risk of type 2 diabetes in the Bangladeshi population.
Lack of association of rs7574865 and rs7601754 SNPs in STAT4 gene with susceptibility to JSLE in Iranian population, despite their association with the risk of adult SLE in the same population, implicates on difference of genetic background of JSLE and SLE.
No significant associations between STAT4 variant and serum neopterin or disease activity parameters were identified. The study confirmed the association of STAT4 rs7574865 polymorphism with rheumatoid arthritis and was the first to indicate an association with rheumatoid factor and anti-cyclic citrullinated peptide antibodies positivity.
5 STAT4 SNPs were tested in 233 patients with established NMOSD and 492 healthy controls. Allelic, additive, dominant, and recessive models identified associations with NMOSD. Minor alleles of 4 STAT4 SNPs exhibited significant association with increased risk of NMOSD: rs7574865 T; rs10181656 G; rs10168266 T; and rs13426947 A in all models. rs7601754 G displayed a protective effect against NMOSD.
data demonstrate that STAT4 plays a role in enabling the normal and timely division of cells undergoing mitosis
IL-23 signaled through both STAT3 and STAT4, and disruption in STAT4 signaling impaired CNS autoimmunity independent of IL-12
these findings show a feed-forward mechanism involving STAT4 and T-BET that modulates the outcome of IL-23 signaling in innate lymphoid cells
The results show that STAT4 plays a critical role in mediating both Th1 and Th2 responses upon immunization with monophosphoryl lipid A.
this study shows that STAT4 regulates the CD8(+) regulatory T cell/T follicular helper cell axis and promotes atherogenesis in insulin-resistant Ldlr(-/-) mice
virus-specific effector and memory CD4 T cells formed independently of Tbet and STAT4, although a slight reduction in the number of antigen-specific CD4 T cells was apparent in mice lacking both transcription factors.
expression associated with early Inflammation in diabetic wounds
STAT4 has a pro-atherogenic role that is at least partially independent of Th1 cell-derived interferon-gamma
Modulation of IL-12/STAT4 signaling may be a valuable therapeutic strategy to preserve islet/beta-cell viability in established diabetes
This study found that stathmin plays an important role in adult hippocampal neurogenesis and spinogenesis. In addition, stathmin mutation led to impaired NMDA receptor-dependent and neurogenesis-associated memory
STAT4 controls GM-CSF production by both Th1 and Th17 cells during experimental autoimmune encephalomyelitis.
Data (including data from studies in knockout mice) suggest Stat4 deletion reduces inflammation in peri-vascular and visceral adipose tissue and this appears to contribute via direct or indirect effects to reduced atheroma formation.
T-bet- and STAT4-dependent IL-33 receptor expression have roles in directly promoting antiviral Th1 cell responses
Primary infections of mice with lymphocytic choriomeningitis virus (LCMV) demonstrated that T cell receptor stimulation induced responsiveness for IFN-gamma and CD25 induction through STAT4-independent pathways.
STAT4 appears to be a critical transcription factor in defense against mycobacterial infection
STAT4 deficiency protects against neointima formation following arterial injury in mice.
IL-12 drives small airway remodeling via STAT4 signaling.
These data demonstrate that STAT4 regulates the respiratory syncytial virus-specific CD8+ T cell response to secondary infection but does not independently regulate lung Th2 or Th17 immune responses.
TCR-induced PD-1 expression was augmented by IL-6 and IL-12, inducers of STAT3 and STAT4 activity
STAT4 is dispensable for antimonial-based chemotherapy.
We have identified STAT4 as a key contributor to insulin resistance and AT inflammation in diet-induced obesity.
These results suggest that the 2 single nucleotide polymorphisms of STAT4 could be used as genetic markers for milk performance traits in Chinese Holstein cows.
The protein encoded by this gene is a member of the STAT family of transcription factors. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. This protein is essential for mediating responses to IL12 in lymphocytes, and regulating the differentiation of T helper cells. Mutations in this gene may be associated with systemic lupus erythematosus and rheumatoid arthritis. Alternate splicing results in multiple transcript variants that encode the same protein.
signal transducer and activator of transcription 4