Recombinant Ubiquitin G76A HUMAN
- Known as:
- Recombinant Ubiquitin G76A HUMAN
- Catalog number:
- REP0028
- Product Quantity:
- 200ug
- Category:
- -
- Supplier:
- DIATHEVA
- Gene target:
- Recombinant Ubiquitin G76A HUMAN
Related genes to: Recombinant Ubiquitin G76A HUMAN
- Gene:
- JAK3 NIH gene
- Name:
- Janus kinase 3
- Previous symbol:
- -
- Synonyms:
- L-JAK, JAKL, LJAK, JAK3_HUMAN, JAK-3
- Chromosome:
- 19p13.11
- Locus Type:
- gene with protein product
- Date approved:
- 1994-12-19
- Date modifiied:
- 2019-04-23
Related products to: Recombinant Ubiquitin G76A HUMAN
Related articles to: Recombinant Ubiquitin G76A HUMAN
- T cell exhaustion remains a barrier to adoptive cell therapies. Although γc cytokines are used to expand T cells, their impact on T cell states remains incompletely defined. Using an in vitro model of repetitive TCR stimulation, we found that high-dose IL-2 or IL-15 promoted exhausted CD8⁺ T cell (TEX) differentiation, with increased inhibitory receptor expression and loss of stem-like features. During chronic LCMV Clone 13 infection, high IL2Rβ expression marked virus-specific CD8⁺ T cells with features of terminally exhausted TEX cells, whereas IL2Rβ deficiency favored progenitor-like populations. In TEX cells, IL-2 and IL-15 preferentially induced STAT5 phosphorylation over other signaling pathways. Genetic disruption of STAT5 similarly supported progenitor subsets, implicating STAT5 in the progression toward more differentiated TEX states under chronic stimulation. We therefore asked whether transient STAT5 attenuation during in vitro T cell expansion could bias differentiation toward progenitor-like populations without compromising functional competence. Transient JAK3 or STAT5 inhibition enriched TCF1⁺Ly108⁺ progenitor-like cells while preserving cytokine production and degranulation capacity. Following transfer into tumor-bearing mice, cells expanded under STAT5-inhibited (STAT5i) conditions mediated superior tumor control and prolonged survival. Likewise, transient STAT5 inhibition preserved memory-progenitor phenotypes in human CD22 CAR T cells without impairing cytotoxicity. RNA sequencing of STAT5i-expanded CD8⁺ T cells confirmed reinforced stem-like transcriptional programs and reduced enrichment of effector and exhausted signatures. Together, these findings identify the IL-2Rβ-STAT5 axis as a regulator of CD8⁺ T cell differentiation and support transient STAT5 modulation during ex vivo expansion to improve therapeutic T cell products. - Source: PubMed
Publication date: 2026/07/22
Shourian MitraBourdin BenoîteEl-Hachem NehmeRuisseaux ClémenceVallée AlexisBallestero Vidal ArnauGingras OlivierRoméro HugoKwarteng Edward OHaddad ÉlieLavallée Vincent-PhilippeBeltra Jean-ChristopheDecaluwe Hélène - Bitter taste receptors are distributed in various non-taste tissues and cells, where they exert crucial roles in neuroimmune regulation and inflammatory response. In this study, a mouse model of fine particle (FPs) exposure was established by nebulized ovalbumin (OVA) inhalation to investigate the effects of FPs on renal function and structure. The experiment results revealed that inhalation of OVA led to glomerular atrophy, and renal tubular epithelial cell swelling and vacuolization, accompanied by increased levels of blood urea nitrogen and creatinine in the bloodstream. OVA inhalation induced a significant elevation in the levels of HO and malondialdehyde (MDA), while significantly decreased the activity of total superoxide dismutase (T-SOD) and the content of glutathione (GSH) in renal tissues. Furthermore, OVA downregulated Th1 cytokine IFN-γ, upregulated Th2 cytokines IL-4, IL-5 and IL-13, and activated pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) as well as genes involved in inflammatory pathways (TLR-2, TLR-4, MyD88, NF-κB, JAK-1, JAK-2, JAK-3, STAT-3, STAT-6). Notably, OVA-induced kidney injury was accompanied by the downregulation of bitter taste receptors and their downstream signaling molecules (α-gustducin, transient receptor potential melastatin 5 [Trpm5]). However, gavage administration of multi-strain probiotics significantly alleviated the toxic effects of OVA on the mouse kidneys, as evidenced by the reversal of the aforementioned abnormal changes in renal structure, biochemical indicators, oxidative stress markers, inflammatory factors, and bitter taste transduction-related molecules. Collectively, these findings indicate that OVA-induced distal organ injury, particularly renal injury, is associated with systemic inflammation and the inhibition of bitter taste transduction pathways. The protective effect of multi-strain probiotics on OVA-inhaled mice is correlated with the activation of bitter taste transduction, as well as the regulation of immune balance and inflammatory responses. - Source: PubMed
Publication date: 2026/07/22
Jiao SiweiZhang RuigangPei YaochenWang MuhuaMa JiePeng XiaoguangYi Huilan - The Janus kinase (JAK) family plays a central role in regulating inflammation and fibrosis through the JAK/STAT signaling pathway, making it an attractive therapeutic target for immune-mediated diseases. In the present study, structural modifications of the quinazoline core were systematically explored to identify potent JAK inhibitors. A CXCL10-based screening strategy identified compound 22a as a promising lead, exhibiting strong inhibitory activity in HaCaT cells with an IC value of 308 nM. Subsequent kinase assays demonstrated that compound 22a exhibits higher inhibitory potency toward JAK1 (IC = 37.86 nM) compared to JAK2 (IC = 102.5 nM), JAK3 (IC = 69.35 nM), and TYK2 (IC = 2142 nM). Mechanistic studies revealed a dose-dependent suppression of STAT1 phosphorylation, confirming inhibition of the JAK1/2-STAT1 signaling pathway. In addition, molecular docking and molecular dynamics simulations were performed to elucidate and validate the binding mode of compound 22a within the JAK1 active site. Collectively, these results indicate that the developed quinazoline derivatives represent promising leads for the further development of selective JAK1 inhibitors. - Source: PubMed
Publication date: 2026/05/26
Gaybullaev ShukhratShi MiaoMiaoZang DengYang ShanYan JialeShakarov SardorTakhirov YuldashTurgunov DavronJiang LiyinZhao JiangyuBozorov KhurshedNiu Chao - To identify therapeutic candidates for IgG4-related sialadenitis, a manifestation of IgG4-related disease characterized by IgG4-positive plasma cell infiltration and limited treatment options beyond glucocorticoids, using transcriptomic profiling and in silico drug repurposing. - Source: PubMed
Publication date: 2026/07/13
Yamamoto MotohisaKamekura RyutaUehara MasaakiIchii YutaTakano Kenichi - Dermatomyositis (DM) is characterized by activation of cytokine pathways that signal through the Janus kinase/signal transducer and activator of transcription (JAK/STAT) axis, although the relative contribution of individual JAK family members remains unclear. Peripheral blood mononuclear cells were isolated from patients with active DM (n = 5), rheumatoid arthritis (RA, n = 7), systemic sclerosis (SSc, n = 7), and healthy donors (HD, n = 5). Phosphorylated STAT3 (pSTAT3) levels were assessed by flow cytometry in CD4+ and CD14+ cells under basal conditions and following selective inhibition of JAK1 (abrocitinib), JAK2 (gandotinib), JAK3 (decernotinib), or TYK2 (deucravacitinib). Under basal conditions, DM displayed the highest pSTAT3 levels in CD4+ cells (median 38.3%), significantly exceeding those observed in HDs (0.9%, P < 0.05) and SSc (8.6%, P < 0.05), while RA showed intermediate levels (17.7%). CD14+ cells from DM patients also demonstrated increased pSTAT3 compared with HDs (9.7% vs 1.4%, P < 0.05), without significant differences versus RA or SSc. Selective JAK inhibition revealed distinct disease-specific patterns. In DM, only TYK2 inhibition significantly reduced pSTAT3 levels in both CD4+ and CD14+ cells (P < 0.05), whereas in RA, pSTAT3 was modulated by inhibition of multiple JAK family members. No significant effects were observed in HDs or SSc patients. These findings identify a selective TYK2-dependent STAT3 activation signature in circulating immune cells from patients with DM, distinguishing this disease from other autoimmune conditions and supporting TYK2 as a potential therapeutic target in DM. - Source: PubMed
Fornaro MDel Vescovo SCacciapaglia FGirolamo FBizzoca RNatuzzi DIannone F