Syk t cell

Immune cell activation triggers signaling cascades leading to transcriptional reprogramming, but also strongly impacts on the cell's metabolic activity to provide energy and biomolecules for inflammatory and proliferative responses. Macrophages activated by microbial pathogen-associated molecular patterns and cytokines upregulate expression of the enzyme ACOD1 that generates the immune-metabolite itaconate by decarboxylation of the TCA cycle metabolite cis-aconitate. Itaconate has anti-microbial as well as immunomodulatory activities, which makes it attractive as endogenous effector metabolite fighting infection and restraining inflammation...

The management of immune thrombocytopenia (ITP) and the prediction of patient response to therapy still represent a significant and constant challenge in hematology. ITP is a heterogeneous disease with an unpredictable evolution. Although the pathogenesis of ITP is currently better known and its etiology has been extensively studied, up to 75% of adult patients with ITP may develop chronicity, which represents a significant burden on patients' quality of life. A major risk of ITP is bleeding, but knowledge on the exact relationship between the degree of thrombocytopenia and bleeding symptoms, especially at a lower platelet count, is lacking...

SARS-CoV-2 infection triggers extensive host immune reactions, leading to severe diseases in certain individuals. However, the molecular basis underlying the excessive yet non-productive immune responses in severe COVID-19 remains incompletely understood. In this study, we conducted a comprehensive analysis of the peripheral blood mononuclear cell (PBMC) proteome and phosphoproteome in sepsis patients positive or negative for SARS-CoV-2 infection, as well as healthy subjects, using quantitative mass spectrometry...

Although in vivo extracellular microenvironments are dynamic, most in vitro studies are conducted under static conditions. Here, we exposed diffuse large B-cell lymphoma (DLBCL) cells to gradient increases in the concentration of hydrogen peroxide (H2 O2 ), thereby capturing some of the dynamics of the tumour microenvironment. Subsequently, we measured the phosphorylation response of B-cell receptor (BCR) signalling proteins CD79a, SYK and PLCγ2 at a high temporal resolution via single-cell phospho-specific flow cytometry...

BACKGROUND: Glioblastomas (GBMs) are central nervous system tumors that resist standard of care interventions and even immune checkpoint blockade. Myeloid cells in the tumor microenvironment can contribute to GBM progression; therefore, emerging immunotherapeutic approaches include reprogramming these cells to achieve desirable anti-tumor activity. Triggering receptor expressed on myeloid cells 2 (TREM2) is a myeloid signaling regulator that has been implicated in a variety of cancers and neurological diseases with contrasting functions, but its role in GBM immunopathology and progression is still under investigation...

Immunosuppressive myeloid cells hinder immunotherapeutic efficacy in tumors, but the precise mechanisms remain undefined. Here, by performing single-cell RNA sequencing in colorectal cancer tissues, we found tumor-associated macrophages and granulocytic myeloid-derived suppressor cells increased most compared to their counterparts in normal tissue and displayed the highest immune-inhibitory signatures among all immunocytes. These cells exhibited significantly increased expression of immunoreceptor tyrosine-based inhibitory motif-bearing receptors, including SIRPA...

ETHNOPHARMACOLOGICAL RELEVANCE: Tetrastigma hemsleyanum is an endemic Chinese herb with a wide range of pharmacological activities, including anti-inflammatory, antiviral, antioxidant, antitumor, and immunomodulatory activities. However, the effect and mechanisms of the anti-inflammatory activity of T. hemsleyanum root extract against dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) have not yet been fully investigated. AIM OF THE STUDY: This study aimed to explore the therapeutic effect and molecular mechanisms of T...

Swine dysentery, spirochetal colitis, and salmonellosis are production-limiting enteric diseases of global importance to the swine industry. Despite decades of efforts, mitigation of these diseases still relies on antibiotic therapy. A common knowledge gap among the 3 agents is the early B-cell response to infection in pigs. Thus, this study aimed to characterize the porcine B-cell response to Brachyspira hyodysenteriae, Brachyspira hampsonii (virulent and avirulent strains), Brachyspira pilosicoli, and Salmonella Typhimurium, the agents of the syndromes mentioned above...

ETHNOPHARMACOLOGICAL RELEVANCE: Curcuma longa, known as turmeric, is an herbaceous perennial plant belonging to the genus Curcuma. It is dispersed throughout tropical and subtropical regions worldwide. Since ancient times, turmeric has been used as an ethnomedicinal plant in the Ayurvedic system, particularly in Asian countries. Rhizomes of turmeric possess several pharmacological properties that give high value as a medicinal remedy for treating a range of conditions, including inflammation, pain, allergies, and digestive issues...

Cross-presentation of dead cell-associated antigens by conventional dendritic cells type 1 (cDC1s) is critical for CD8+ T cells response against many tumors and viral infections. It is facilitated by DNGR-1 (CLEC9A), an SYK-coupled cDC1 receptor that detects dead cell debris. Here, we report that DNGR-1 engagement leads to rapid activation of CBL and CBL-B E3 ligases to cause K63-linked ubiquitination of SYK and terminate signaling. Genetic deletion of CBL E3 ligases or charge-conserved mutation of target lysines within SYK abolishes SYK ubiquitination and results in enhanced DNGR-1-dependent antigen cross-presentation...

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a common complication of Type 2 diabetes mellitus (T2DM), which frequently results in disabling neuropathic pain and lower-limb amputation. The identification of noninvasive biomarkers for DPN may help early detection and individualized treatment of DPN. METHODS: In this study, we identified differentially expressed genes (DEGs) between DPN and the control based on blood-source (GSE95849) and tissue-source gene expression profiles (GSE143979) from the Gene Expression Omnibus (GEO) database using limma, edgeR, and DESeq2 approaches...

PURPOSE: The transmembrane protein CD37 is expressed almost exclusively in lymphoid tissues, with the highest abundance in mature B cells. CD37-directed antibody- and, more recently, cellular-based approaches have shown preclinical and promising early clinical activity. Naratuximab emtansine (Debio 1562, IMGN529) is an antibodydrug conjugate (ADC) that incorporates an anti-CD37 monoclonal antibody conjugated to the maytansinoid DM1 as payload. Naratuximab emtansine has shown activity as a single agent and in combination with the anti-CD20 monoclonal antibody rituximab in B cell lymphoma patients...

Kappa-carrageenan (KCG), which is used to induce thrombosis in laboratory animals for antithrombotic drug screening, can trigger platelet aggregation. However, the cell-surface receptor and related signaling pathways remain unclear. In this study, we investigated the molecular basis of KCG-induced platelet activation using light-transmittance aggregometry, flow cytometry, western blotting, and surface plasmon resonance assays using platelets from platelet receptor-deficient mice and recombinant proteins. KCG-induced tail thrombosis was also evaluated in mice lacking the platelet receptor...

BACKGROUND: Methotrexate (MTX), sulfonamides, hydroxychloroquine, and leflunomide have consistently resulted in remission with relatively mild to moderate adverse effects in patients with rheumatoid arthritis (RA). Modern medications outperform traditional treatments in that they target the pathological processes that underlie the development of RA. METHODS: Following PRISMA guidelines, the authors accomplished a systematic review of the clinical efficacy of RA drugs, including the biologics such as Tumor Necrosis Factor-alpha inhibitors (TNF-α i) like Etanercept, Infliximab, Golimumab, and Adalimumab, kinase inhibitors (JAK inhibitors including Baricitinib and Tofacitanib), SyK inhibitors like Fos-tamatinib, MAPK inhibitors such as Talmapimod, T-cell inhibitors (Abatacept), IL6 blockers (Tocilizumab), and B cells depleters (Rituximab)...

BACKGROUND AND OBJECTIVE: Due to the suboptimal therapeutic efficacy and potential adverse effects associated with traditional immunosuppressive medications, there has been an increasing emphasis on the development and utilization of immunotherapies. This paper aims to provide clinicians with valuable insights for selecting appropriate therapeutic approaches and contribute to the development of novel immunotherapeutic drugs. MAIN BODY: This paper categorizes the immunotherapeutic drugs that are used for the treatment of immune-mediated glomerular diseases into three groups: immunotherapies targeting antigen-presenting cells (anti-CD80), immunotherapies targeting T/B cells (anti-CD20, anti-CD22, BAFF and APRIL inhibitors, CD40-CD40L inhibitors, proteasome inhibitors, Syk inhibitors, and Btk inhibitors), and immunotherapies targeting the complement system (C5 inhibitors, C5a/C5aR inhibitors, C3 inhibitors, MASP2 inhibitors, factor B inhibitors, and factor D inhibitors)...

With the development of immunotherapy, the process of tumor treatment is also moving forward. Polysaccharides are biological response modifiers widely found in plants, animals, fungi, and algae and are mainly composed of monosaccharides covalently linked by glycosidic bonds. For a long time, polysaccharides have been widely used clinically to enhance the body's immunity. However, their mechanisms of action in tumor immunotherapy have not been thoroughly explored. Dendritic cells (DCs) are a heterogeneous population of antigen presenting cells (APCs) that play a crucial role in the regulation and maintenance of the immune response...

Increased prevalence of cancer in obese individuals is involved with dyslipidemia- induced chronic inflammation and immune suppression. Although apolipoprotein C-III (ApoC3)-transgenic mice (ApoC3TG mice) or poloxamer 407 (P407)-treated mice had hyperlipidemia, CD8+ T cells with upregulated antitumor activities were observed in ApoC3TG mice, and decreased CD8+ T cell activities were observed in P407-treated mice. Increased ApoC3 expression in hepatocellular carcinoma was associated with increased infiltration of CD8+ T cells and predicted survival...

The tumor microenvironment (TME) provides excellent conditions for the development of glioma. The present study sought to identify the prognostic factors of glioma that could be used to improve the prognosis of patients with this disease. In the present study, Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) and Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data calculations were employed to estimate the ratio of tumor-infiltrating immune cells and the quantity of immune and stromal components in 698 glioma cases from the Cancer Genome Atlas database...

Visual impairment is occasionally observed in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Although uveitis and optic neuritis have been reported in MS and EAE, the precise mechanisms underlying the pathogenesis of these visual impairments remain poorly understood. This study aims to identify differentially expressed genes (DEGs) in the retinas of mice with EAE to identify genes that may be implicated in EAE-induced visual impairment. Fourteen adult mice were injected with myelin oligodendrocyte glycoprotein35-55 to induce the EAE model...

Warm autoimmune hemolytic anemia (wAIHA) is a rare acquired autoimmune disease mediated by antibodies targeting red blood cells. The involvement of CD4 T helper (Th) cells has been scarcely explored, with most findings extrapolated from animal models. Here, we performed quantification of both effector T lymphocytes (Teff) and regulatory T cells (Treg), associated with functional and transcriptomic analyses of Treg in human wAIHA. We observed a shift of Teff toward a Th17 polarization concordant with an increase in serum IL-17 concentration that correlates with RBC destruction parameters, namely LDH and bilirubin levels...