Rabbit Anti-Human STAT4 (Phospho-Tyr693) polyclonal antibody

The H3K4me3 demethylase Kdm5a regulates gene transcription and is implicated in carcinogenesis. However, the role of Kdm5a in innate immune response remains poorly understood. Here, we demonstrate that Kdm5a deficiency impairs activation of natural killer (NK) cells, with decreased IFN-gamma production. Accordingly, Kdm5a(-/-) mice are highly susceptible to Listeria monocytogenes (Lm) infection. During NK cell activation, loss of Kdm5a profoundly impairs phosphorylation and nuclear localization of STAT4, along with increased expression of suppressor of cytokine signaling 1 (SOCS1). Mechanistic studies reveal that Kdm5a associates with p50 and binds to the Socs1 promoter region in resting NK cells, leading to a substantial decrease in H3K4me3 modification and repressive chromatin configuration at the Socs1 promoter. Thus, Kdm5a is required for priming activation of NK cells by suppressing the suppressor, SOCS1. Our study provides insights into the epigenetic regulation of innate immune response of NK cells.

Rheumatoid arthritis (RA) is a systemic autoimmune disease in whose etiology genetic factors are known to play an important role. Among the genes associated with RA, STAT4 could be an important factor in conducting helper T cells toward the pro-inflammatory Th1 and Th17 lineages. The aim of this study is to determine the association of the STAT4 polymorphism rs7574865 with RA, disease activity, and anti-cyclic citrullinated peptide (CCP) antibody levels in a Mexican population. Genotyping was carried out using the TaqmanA (R) system from Applied Biosystems in 140 patients with RA and 150 healthy subjects. Disease activity was evaluated by a rheumatologist using the DAS28 and Spanish-HAQ-DI instruments. Anti-CCP levels were determined by ELISA. Associations of the genotypes of rs7574865 with DAS28, HAQ, and anti-CCP antibody levels with RA were determined. Findings showed that the GT and TT genotypes and the T allele from rs7574865 were all associated as risk factors for RA, independently of their anti-CCP status. An association with moderate-to-high disease activity (DAS28 >= 3.2) was also found. Additionally, patients with the GT or TT genotypes showed lower HAQ values than those who carried the GG genotype. No differences in anti-CCP antibody levels or DAS28 and genotypes were found. This work supports the association of the STAT4 rs7574865 polymorphism with RA and disease activity, but not with anti-CCP antibody levels in a Mexican population.