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B Cell Lymphoma Immunotherapy Using TLR9-Targeted Oligonucleotide STAT3 Inhibitors.

Growing evidence links the aggressiveness of non-Hodgkin's lymphoma, especially the activated B cell-like type diffuse large B cell lymphomas (ABC-DLBCLs) to Toll-like receptor 9 (TLR9)/MyD88 and STAT3 transcription factor signaling. Here, we describe a dual-function molecule consisting of a clinically relevant TLR9 agonist (CpG7909) and a STAT3 inhibitor in the form of a high-affinity decoy oligodeoxynucleotide (dODN). The CpG-STAT3dODN blocked STAT3 DNA binding and activity, thus reducing expression of downstream target genes, such as MYC and BCL2L1, in human and mouse lymphoma cells. We fur

A Type I Interferon and IL-10 Induced by Orientia tsutsugamushi Infection Suppresses Antigen-Specific T Cells and Their Memory Responses.

Despite the various roles of type I interferon (type I IFN) responses during bacterial infection, its specific effects in vivo have been poorly characterized in scrub typhus caused by Orientia tsutsugamushi infection. Here, we show that type I IFNs are primarily induced via intracellular nucleic acids sensors, including RIG-I/MAVS and cGAS/STING pathways, during O. tsutsugamushi invasion. However, type I IFN signaling did not significantly affect pathogenesis, mortality, or bacterial burden during primary infection in vivo, when assessed in a mice model lacking a receptor for type I IFNs (IFNA

Enterovirus-71 virus-like particles induce the activation and maturation of human monocyte-derived dendritic cells through TLR4 signaling.

Enterovirus 71 (EV71) causes seasonal epidemics of hand-foot-and-mouth disease and has a high mortality rate among young children. We recently demonstrated potent induction of the humoral and cell-mediated immune response in monkeys immunized with EV71 virus-like particles (VLPs), with a morphology resembling that of infectious EV71 virions but not containing a viral genome, which could potentially be safe as a vaccine for EV71. To elucidate the mechanisms through which EV71 VLPs induce cell-mediated immunity, we studied the immunomodulatory effects of EV71 VLPs on human monocyte-derived dendr

Allogeneic mesenchymal stem cells do not protect NZBxNZW F1 mice from developing lupus disease.

Mesenchymal stem cell (MSC) therapy has shown promise clinically in graft-versus-host disease and in preclinical animal models of T helper type 1 (Th1)-driven autoimmune diseases, but whether MSCs can be used to treat autoimmune disease in general is unclear. Here, the therapeutic potential of MSCs was tested in the New Zealand black (NZB)xNew Zealand white (NZW) F1 (NZB/W) lupus mouse model. The pathogenesis of systemic lupus erythematosus involves abnormal B and T cell activation leading to autoantibody formation. To test whether the immunomodulatory activity of MSCs would inhibit the develo

Class II-restricted T cell responses in Theiler's murine encephalomyelitis virus-induced demyelinating disease. V. Mapping of a dominant immunopathologic VP2 T cell epitope in susceptible SJL/J mice.

Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease is a relevant mouse model of multiple sclerosis. Demyelination is linked to persistent TMEV infection of the central nervous system and characterized by perivascular inflammatory mononuclear infiltrates and primary demyelination. Myelin damage is a T cell-dependent process and susceptibility correlates with the temporal development of chronic virus-specific delayed-type hypersensitivity (DTH) responses. Our previous results have shown that inflammatory processes mediated by Th1 cells specific for a determinant(s) on …

Characteristics of peripheral blood NK and NKT-like cells in euthyroid and subclinical hypothyroid women with thyroid autoimmunity experiencing reproductive failure.

Thyroid autoimmunity (TAI) appears to play a crucial role in female infertility, recurrent pregnancy loss and IVF failure. Thyroid autoantibodies against thyroid peroxidase and thyroglobulin have been shown to represent an independent risk factor for infertility and miscarriage. Moreover, thyroxin hormone administration reduces the risk of obstetrical complications in TAI positive women. The aim of our present study was to investigate the immunological background of female infertility and recurrent pregnancy loss in euthyroid and subclinical hypothyroid women with TAI focusing on innate immuni

The role of CD4+ and CD8+ T cells in the protective inflammatory response to a pulmonary cryptococcal infection.

Moderately virulent strains of Cryptococcus neoformans, inoculated via the trachea, cause a pulmonary infection in BALB/c mice that was gradually resolved by T lymphocyte-dependent mechanisms. The current studies, using monoclonal antibodies to deplete T cell subsets, demonstrated that CD4+ and CD8+ T cells combined to mediate a prominent pulmonary inflammatory infiltrate that included lymphocytes, macrophages, neutrophils, and eosinophils. The inflammatory response peaked 2 weeks after infection and coincided with the beginning of gradual pulmonary clearance of the infection. CD4/CD8 double d

Design and synthesis of RNA vaccines encoding SAG1 antigen of toxoplasma gondii and evaluation of immunogenicity and its protective efficacy against acute toxoplasmosis in BALB/c mice.

Toxoplasmosis represents a significant global health concern due to the limited availability of safe and effective vaccines and drugs. mRNA technology offers a promising approach for toxoplasmosis vaccine development, combining effectiveness with enhanced safety features. Unlike DNA vaccines, mRNA vaccines remain exclusively in the cytoplasm, eliminating the risk of genomic integration and malignant cell transformation. We designed an RNA-based vaccine encoding the T. gondii SAG1 gene and validated its protein expression in vitro using Western blotting and indirect fluorescent antibody testing

Effects of Different Routes and Forms of Vitamin D Administration on Mesenteric Lymph Node CD4+ T Cell Polarization and Intestinal Injury in Obese Mice Complicated with Polymicrobial Sepsis.

This study compared the efficacies of enteral cholecalciferol and/or intravenous (IV) calcitriol administration on mesenteric lymph node (MLN) cluster-of-differentiation-4-positive (CD4+) T cell distribution and intestinal barrier damage in obese mice complicated with sepsis. Mice were fed a high-fat diet for 16 weeks and then sepsis was induced by cecal ligation and puncture (CLP). Mice were divided into the following sepsis groups: without vitamin D (VD) (S); with oral cholecalciferol 1 day before CLP (G); with IV calcitriol 1 h after CLP (V); and with both cholecalciferol before and IV calc

Nucleosomal histone proteins of L. donovani: a combination of recombinant H2A, H2B, H3 and H4 proteins were highly immunogenic and offered optimum prophylactic efficacy against Leishmania challenge in hamsters.

The present study includes cloning and expression of recombinant Leishmania donovani histone proteins (rLdH2B, rLdH3, rLdH2A and rLdH4), assessment of their immunogenicity in Leishmania infected cured patients/endemic contacts as well as in cured hamsters and finally evaluation of their prophylactic efficacy in hamsters against L. donovani challenge. All recombinant proteins were expressed and purified from the heterologous bacterial host system. Leishmania infected cured patients/endemic contacts as well as cured hamsters exhibited significantly higher proliferative responses to individual re

Disturbed tryptophan metabolism in cardiovascular disease.

Atherosclerosis (AS), a major pathologic consequence of obesity, is the main etiological factor of cardiovascular disease (CVD), which is the most common cause of death in the western world. A systemic chronic low grade immune- mediated inflammation (scLGI) is substantially implicated in AS and its consequences. In particular, proinflammatory cytokines play a major role, with Th1-type cytokine interferon-γ (IFN-γ) being a key mediator. Among various other molecular and cellular effects, IFN-γ activates the enzyme indoleamine 2,3-dioxygenase (IDO) in monocyte-derived macrophages, dendritic, and

Peripheral lymphocyte remodeling following sound-based anxiety intervention: prominent alterations in γδ T-cell subsets.

In the context of the COVID-19 pandemic, closed school management has resulted in college students being more prone to anxiety. As a means of stress reduction, music therapy has been widely used as an adjunctive treatment for anxiety disorders and other psychotic disorders. Some studies have shown that music can influence the immune function, however, there is still a lack of comprehensive research on the effects of the increasingly sophisticated music therapy on the function of the immune system. A healthy immune system and a good mood are closely related; therefore, the purpose of this study

Mechanism of Babao Dan on fluorouracil-induced bone marrow suppression and T cell immune disorder through MAPK pathway.

Babao Dan (BBD), a traditional Chinese herbal compound, has demonstrated significant antitumor effects and is clinically used as an adjunctive therapy for various gastrointestinal malignancies. However, its underlying mechanisms of action remain poorly understood. This study aimed to investigate the effects of BBD on 5-fluorouracil (5-FU)-induced myelosuppression and T-lymphocyte subpopulation alterations, and to explore its mechanism in ameliorating cellular immune dysfunction caused by myelosuppression via the MAPK signaling pathway. The major constituents of BBD are fatty acids, triterpenoi

Overexpression, clinical significance and potential mechanisms of protein kinase D1 in hepatocellular carcinoma: multi-omic analyses and pharmacological insights.

Protein kinase D1 (PRKD1), a serine/threonine kinase of the PKD family, has been implicated in tumor biology, but its role in hepatocellular … and myeloid-derived suppressor cells (MDSCs), and negative correlations with CD8+ T cells and CD4+ Th1 cells, suggesting an immunosuppressive role. Mechanistic experiments demonstrated that conditioned medium from PRKD1-knockdown HCC cells promoted M1 polarization and reduced M2 markers in THP-1 cells, while PRKD1 silencing increased PD-L1 and IDO1 express …

Type III interferon inhibits bladder cancer progression by reprogramming macrophage-mediated phagocytosis and orchestrating effective immune responses.

BACKGROUND: Interferons (IFNs) are essential for activating an effective immune response and play a central role in immunotherapy-mediated i … Ifnl3 expression in tumor cells significantly increased the infiltration of cytotoxic CD8+ T cells, Th1 cells, natural killer cells, proinflammatory macrophages, and dendritic cells, but reduced neutrophil infiltration. Transcriptomic analyses revealed significant upregulation of many genes associated with effective immune response, including lymphocyte rec …

Serum amyloid A1 induced dysfunction of airway macrophages via CD36 pathway in allergic airway inflammation.

Previous studies showed that serum amyloid A (SAA) and macrophages were associated with allergic airway inflammation. However, the interaction between SAA1 and macrophages in allergic airway inflammation remains to be further elucidated. In this study, the levels of SAA1 were measured in nasal tissues from patients with eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP), house dust mite (HDM)-treated BEAS-2B cells and the tissues of mice of HDM-induced allergic airway inflammation. Human monocytes-derived macrophages and mouse bone marrow-derived macrophages (BMDMs) were exposed to

Emerging Role of Immunomonitoring to Predict the Clinical Outcome of Patients With Malignant Pleural Mesothelioma Treated With Radical Radiation Therapy.

PURPOSE: The present study aimed at evaluating the baseline immune profile and the immunomodulating effects of radical hemithoracic radiatio … lliative treatment, in particular an improvement in activated T cells and in interferon-γ-producing Th1 cells after RT. In the interventional arm, baseline high levels of Th22 and IL-10 and an increase in T cells were associated with an improved survival, whereas a fold increase in serum mesothelin correlated with the development of severe toxicity. An impr …

T Cell Subsets in Graft Versus Host Disease and Graft Versus Tumor.

Allogeneic hematopoietic cell transplantation (allo-HCT) is an essential therapeutic modality for patients with hematological malignancies and other blood disorders. Unfortunately, acute graft-versus-host disease (aGVHD) remains a major source of morbidity and mortality following allo-HCT, which limits its use in a broader spectrum of patients. Chronic graft-versus-host disease (cGVHD) also remains the most common long-term complication of allo-HCT, occurring in reportedly 30-70% of patients surviving more than 100 days. Chronic GVHD is also the leading cause of non-relapse mortality (NRM) occ

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… Interferon gamma (IFNγ), a primary mediator of inflammation and tissue damage, is a primary product of activated Th1 cells ( 45 ). The defining Th1 transcription factor is T-box expressed in T cells (T-bet or Tbx21) ( 46 ). … The IFNγ secreted by donor Th1 cells have been found to both encourage further Th1 cell differentiation and direct damage to the gut mucosa ( 48 ). Preclinical models have shown elevation of Th1-derived cytokines including tumor necrosis factor (TNF) and IFNγ in association with GVHD. …

Subsets of mononuclear phagocytes are enriched in the inflamed colons of patients with IBD.

BACKGROUND: Myeloid cells, especially mononuclear phagocytes, which include monocytes, macrophages and dendritic cells (DC), play vital roles in innate immunity, and in the initiation and maintenance of adaptive immunity. While T cell-associated activation pathways and cytokines have been identified and evaluated in inflammatory bowel disease (IBD) patients (Neurath, Nat Rev Gastroenterol Hepatol 14:269-78, 1989), the role of mononuclear phagocytes are less understood. Recent reports support the crucial role of DC subsets in the development of acute colitis models (Arimura et al., Mucosal Immu

Effects of umbilical cord blood cells, and subtypes, to reduce neuroinflammation following perinatal hypoxic-ischemic brain injury.

BACKGROUND: It is well understood that hypoxic-ischemic (HI) brain injury during the highly vulnerable perinatal period can lead to cerebral palsy, the most prevalent cause of chronic disability in children. Recently, human clinical trials have reported safety and some efficacy following treatment of cerebral palsy using umbilical cord blood (UCB) cells. UCB is made up of many different cell types, including endothelial progenitor cells (EPCs), T regulatory cells (Tregs), and monocyte-derived suppressor cells (MDSCs). How each cell type contributes individually towards reducing neuroinflammati