NFAT5 antibody (FITC)
- Known as:
- NFAT5 (anti-) (fluorecein)
- Catalog number:
- orb3360
- Product Quantity:
- 100 ug
- Category:
- -
- Supplier:
- Biorb
- Gene target:
- NFAT5 antibody (FITC)
Related genes to: NFAT5 antibody (FITC)
- Gene:
- NFAT5 NIH gene
- Name:
- nuclear factor of activated T cells 5
- Previous symbol:
- -
- Synonyms:
- TONEBP, KIAA0827, NFATL1, OREBP, NFATZ, NF-AT5
- Chromosome:
- 16q22.1
- Locus Type:
- gene with protein product
- Date approved:
- 1999-07-16
- Date modifiied:
- 2019-04-23
Related products to: NFAT5 antibody (FITC)
Related articles to: NFAT5 antibody (FITC)
- CD8 T cell exhaustion is a conserved differentiation program induced by persistent antigen stimulation and originally characterized in chronic infection. In cancer, this program is actively reinforced and stabilized by the tumor microenvironment. Here, we examine how tumors convert a physiological adaptation to chronic stimulation into a deeply entrenched dysfunctional state. Sustained TCR signaling initiates exhaustion through NFAT- and TOX-dependent transcriptional remodeling, but tumor-specific extrinsic pressures, including hypoxia, metabolic competition, ionic imbalance, mechanical stress, and heterogeneous antigen exposure, amplify and stabilize this program. These environmental cues converge on transcription factor networks such as IRF, BATF, NR4A, and NFAT5, which integrate chronic signaling with stress-adaptive responses and progressively restrict effector potential. Exhaustion in tumors becomes epigenetically imprinted. Exhaustion-specific enhancer landscapes persist despite PD-1 blockade, reflecting a lineage-like state enforced by chromatin remodeling factors such as TOX. Thus, checkpoint inhibition transiently restores function without fully reprogramming cellular identity. We propose that tumor-induced exhaustion arises from the layered convergence of chronic antigen signaling and microenvironmental reinforcement, culminating in chromatin fixation. Understanding this stabilization process reframes therapeutic strategies: effective cancer immunotherapy will likely require combinatorial approaches that target not only inhibitory receptors but also metabolic resilience, stress-sensing pathways, and epigenetic architecture. By dissecting how tumors convert adaptive restraint into durable dysfunction, new avenues may emerge to destabilize exhaustion and restore durable antitumor immunity. - Source: PubMed
Publication date: 2026/06/26
Thouenon RomaneOngaro MarcoVerdeil Grégory - Hyperosmotic stress triggers a complex adaptive response that enables cells to maintain homeostasis and survive osmotic perturbations. However, the molecular mechanisms that coordinate transcriptional and epigenetic programs in response to osmotic stress remain poorly defined. Here, through an unbiased chemical screen, we identify activation of nuclear factor erythroid 2 - related factor 2 (Nrf2) as a potent enhancer of cell survival under hyperosmotic stress. Mechanistically, Nrf2 does not function as a sustained transcriptional activator of osmoprotective genes during stress. Instead, Nrf2 establishes a primed chromatin state prior to osmotic challenge, characterized by increased enrichment of activation-associated histone modifications at osmoprotective loci. This epigenetic priming enables enhanced recruitment of NFAT5 upon hyperosmotic stimulation, thereby amplifying osmoprotective gene transcription. Disruption of Nrf2 abolishes chromatin activation, NFAT5 binding, and transcriptional induction of osmoprotective genes, whereas pharmacological Nrf2 activation restores these processes and improves cell survival. In a model of dehydration-induced hyperosmotic stress, renal cell death was markedly increased in Nrf2-deficient mice, while Nrf2 activation promoted the expression of osmoprotective genes and conferred tissue protection. Together, our findings identify Nrf2 as an epigenetic priming factor that licenses NFAT5 - dependent transcription under hyperosmotic stress, revealing a previously unrecognized chromatin-based mechanism that enhances cellular adaptation to osmotic challenges. - Source: PubMed
Publication date: 2026/06/22
Lu YiLi NaDou XudanZhang ZilingSu YongxuanLi XuetingWang JingTian WeipingSun Shao-KaiZhang LirongChen YupengLiu Zhiheng - Seawater-induced acute lung injury (ALI) shares pathological features with other forms of ALI, characterised by high mortality; however, it presents unique traits, particularly persistent hypoxemia. Nuclear Factor of Activated T cells 5 (NFAT5), initially recognised as a tonicity-responsive enhancer-binding protein, has emerged as acritical regulator of inflammation. Nonetheless, its specific function in alveolar macrophages (AMs) during hyperosmolar seawater-induced ALI remains unclear. This study establishes a murine model of seawater-induced ALI, revealing significantly elevated NFAT5 expression in lung macrophages. Siglec1-specific NFAT5 knockout effectively mitigated seawater-induced lung injury. Mechanistically, NFAT5 was found to directly bind the promoter region of Phosphofructokinase, Platelet type (PFKP) in AMs, enhancing its transcriptional activity. NFAT5 knockdown resulted in downregulation of PFKP expression and suppression of glycolysis, which inhibited M1 macrophage polarisation while promoting M2 macrophage polarisation, thereby reducing the release of inflammatory cytokines. Additional in vitro and in vivo experiments demonstrated that PFKP overexpression counteracts the protective effects of Siglec1-specific NFAT5 knockout in seawater-induced ALI by restoring glycolytic activity. Collectively, these findings illustrate that the NFAT5-PFKP signaling axis in AMs regulates macrophage polarisation and inflammatory responses through glycolytic reprogramming, playing a critical pathogenic role in seawater-induced ALI. These insights enhance understanding of the energy metabolism in AMs, previously regarded as less relevant in inflammation, and identify the NFAT5-PFKP axis as a promising therapeutic target for seawater-induced ALI. - Source: PubMed
Publication date: 2026/06/21
Wang XinxinGuo XianWang YifengGao YonghengWang LinFang YanfengGao FuguoYuan FangrunGao BoyangLi YanYang LeJin Faguang - The corticomedullary osmotic gradient between renal cortex and medulla induces a specific spatial gene expression pattern. The factors controlling these differences have not been fully addressed. A hypertonic environment leads to the activation of nuclear factor of activated T-cells 5 (NFAT5), which regulates the expression of osmoprotective genes. While NFAT5 function under hypertonic conditions has been extensively studied, its contribution to basal gene regulation remains unclear. We used murine principal kidney cortical collecting duct (mpkCCD) cells, induced functional deletion of NFAT5, and performed gene expression profiling to identify genes that are differentially expressed under isotonic and hypertonic cell culture conditions. Hypertonic stress induced extensive transcriptional changes in control cells, which were markedly altered in NFAT5-deficient cells. Furthermore, a comparison of the mpkCCD transcriptomes with gene expression profiles from the renal cortex and inner medulla of control and principal cell-specific NFAT5 knockout mice revealed a partial overlap in hypertonicity-associated and NFAT5-dependent gene expression patterns. In both conditions, the expression of known NFAT5 target genes, like Aqp2 and Ranbp3l, was downregulated. These findings support the use of mpkCCD cells as a complementary model for studying NFAT5-associated gene regulation under controlled in vitro conditions. - Source: PubMed
Engel KristinaChernyakov DmitryPernecker MoritzKaruppusamy ShobikaSchreiber TimmEdemir Bayram - Chronic high sodium intake precipitates vascular aging; however, the molecular signaling remain poorly defined. Nuclear factor of activated T cells 5 (NFAT5) is a central regulator of the cellular osmotic stress response; however, its specific role in modulating vascular senescence signaling remains unknown. Here, we investigated whether NFAT5 signaling mediates high‑sodium-induced vascular aging and evaluated the therapeutic potential of the specific NFAT5 inhibitor KRN5. We utilized C57BL/6 J mice fed a high‑sodium diet and cultured primary vascular smooth muscle cells (VSMCs) under hypertonic conditions to model vascular aging in vivo and in vitro. Mechanistic studies, including RNA sequencing, chromatin immunoprecipitation, and luciferase reporter assays, were performed to identify NFAT5 transcriptional targets. We found high sodium accelerated vascular aging and VSMC senescence, accompanied by a marked upregulation and nuclear activation of NFAT5. KRN5 significantly attenuated these aging phenotypes and suppressed the senescence-associated secretory phenotype (SASP) in vivo. Mechanistically, activated NFAT5 conferred robust apoptosis resistance to senescent VSMCs by shifting the Bcl-2 family balance towards cell survival. Specifically, NFAT5 directly binds to a conserved region of the Bcl-XL promoter to drive its transcription. Consequently, KRN5 effectively re-sensitizing senescent VSMCs to apoptosis. Collectively, our findings identify the NFAT5 signaling pathway as a critical mechanistic link between high sodium intake and vascular aging. KRN5 is a novel senolytic strategy that dismantles the Bcl-XL-dependent survival mechanism in senescent VSMCs. - Source: PubMed
Publication date: 2026/06/04
Bian ShihuiJiang YuYu YijieLi BoDai ZhiyinYuan WeiZhong Wei