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Fish & Shellfish Immunology May 2024CD28 and CD80/86 are crucial co-stimulatory molecules for the T cell activation. Previous study illustrated that CD28 and CD80/86 present on T cells and...
CD28 and CD80/86 are crucial co-stimulatory molecules for the T cell activation. Previous study illustrated that CD28 and CD80/86 present on T cells and antigen-presenting cells in flounder (Paralichthys olivaceus), respectively. The co-stimulatory molecules were closely associated with cell immunity. In this paper, recombinant protein of flounder CD80/86 (rCD80/86) and phytohemagglutinin (PHA) were added to peripheral blood leukocytes (PBLs) in vitro. Lymphocytes were significantly proliferated with CFSE staining, and the proportion of CD4 and CD28 lymphocytes significantly increased. In the meantime, genes related to the CD28-CD80/86 signaling pathway or T cell markers were significantly upregulated (p < 0.05). For further study, the interaction between CD80/86 and CD28 was confirmed. The plasmid of CD28 (pCD28-FLAG and pVN-CD28) or CD80/86 (pVC-CD80/86) was successfully constructed. In addition, pVN-ΔCD28 without the conserved motif "TFPPPF" was constructed. The results showed that bands of pCD28-FLAG bound to rCD80/86 were detected by both anti-FLAG and anti-CD80/86. pVN-CD28 complemented to pVC-CD80/86 showing positive fluorescent signals, and pVN-ΔCD28 failed to combine with pVC-CD80/86. The motif "TFPPPF" in CD28 played a crucial role in this linkage. These results indicate that CD28 and CD80/86 molecules interact with each other, and their binding may modulate T lymphocytes immune response in flounder. This study proved the existence of CD28-CD80/86 signaling pathway in flounder.
Topics: Animals; CD28 Antigens; Lymphocyte Activation; Flounder; B7-1 Antigen; Cell Adhesion Molecules; CD4-Positive T-Lymphocytes
PubMed: 38458503
DOI: 10.1016/j.fsi.2024.109482 -
Cancer Genomics & Proteomics 2024Constitutional chromosomal aberrations are rare in hematologic malignancies and their pathogenetic role is mostly poorly understood. We present a comprehensive molecular...
BACKGROUND/AIM
Constitutional chromosomal aberrations are rare in hematologic malignancies and their pathogenetic role is mostly poorly understood. We present a comprehensive molecular characterization of a novel constitutional chromosomal translocation found in two siblings - sisters - diagnosed with myelodysplastic syndrome (MDS).
MATERIALS AND METHODS
Bone marrow and blood cells from the two patients were examined using G-banding, RNA sequencing, PCR, and Sanger sequencing.
RESULTS
We identified a balanced t(17;19)(q21;p13) translocation in both siblings' bone marrow, blood cells, and phytohemagglutinin-stimulated lymphocytes. The translocation generated a MYO1F::WNK4 chimera on the der(19)t(17;19), encoding a chimeric serine/threonine kinase, and a VPS25::MYO1F on the der(17), potentially resulting in an aberrant VPS25 protein.
CONCLUSION
The t(17;19)(q21;p13) translocation found in the two sisters probably predisposed them to myelodysplasia. How the MYO1F::WNK4 and/or VPS25::MYO1F chimeras, perhaps especially MYO1F::WNK4 that encodes a chimeric serine/threonine kinase, played a role in MDS pathogenesis, remains incompletely understood.
Topics: Humans; Myelodysplastic Syndromes; Translocation, Genetic; Female; Siblings; Chromosomes, Human, Pair 17; Chromosomes, Human, Pair 19; Protein Serine-Threonine Kinases; Vesicular Transport Proteins; Oncogene Proteins, Fusion; Middle Aged
PubMed: 38670586
DOI: 10.21873/cgp.20446 -
Immunobiology Jan 2024Multipotent mesenchymal stromal cells (MSCs) have demonstrated a pronounced immunosuppressive activity, the manifestation of which depends on the microenvironmental...
Multipotent mesenchymal stromal cells (MSCs) have demonstrated a pronounced immunosuppressive activity, the manifestation of which depends on the microenvironmental factors, including O level. Here we examined the effects of MSCs on transcriptomic profile of allogeneic phytohemagglutinin-stimulated peripheral blood mononuclear cells (PBMCs) after interaction at ambient (20%) or "physiological" hypoxia (5%) O. As revealed with microarray analysis, PBMC transcriptome at 20% O was more affected, which was manifested as differential expression of more than 300 genes, whereas under 5% O 220 genes were changed. Most of genes at 20% O were downregulated, while at hypoxia most of genes were upregulated. Altered gene patterns were only partly overlapped at different O levels. A set of altered genes at hypoxia only was of particular interest. According to Gene Ontology a part of above genes was responsible for adhesion, cell communication, and immune response. At both oxygen concentrations, MSCs demonstrated effective immunosuppression manifested as attenuation of T cell activation and proliferation as well as anti-inflammatory shift of cytokine profile. Thus, MSC-mediated immunosuppression is executed with greater efficacy at a "physiological" hypoxia, since the same result has been achieved through a change in the expression of a fewer genes in target PBMCs.
Topics: Humans; Transcriptome; Leukocytes, Mononuclear; Mesenchymal Stem Cells; Cell Communication; Hypoxia; Cells, Cultured; Cell Proliferation
PubMed: 38091798
DOI: 10.1016/j.imbio.2023.152766 -
Frontiers in Bioscience (Landmark... Feb 2024Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by immune response mediated islet beta cells destruction. However, the mechanisms that cause... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by immune response mediated islet beta cells destruction. However, the mechanisms that cause immune response in TIDM are still under investigation. Therefore, the goal of this study was to investigate the role of advanced glycation end products (AGEs) in the regulation of the immune response in peripheral blood mononuclear cells (PBMCs) from patients with T1DM.
METHODS
PBMCs isolated from T1DM patients and control subjects were used in the current study. Cytokines, AGEs related to glyoxalase 1 (GLO1), methylglyoxal (MG)-derived AGEs were assessed longitudinally.
RESULTS
The results of published T1DM PBMC microarray datasets using random-effects meta-analysis models revealed immune responses in the PBMCs of patients with T1DM compared with control subjects. Moreover, the activity of GLO1, which is the key MG-metabolizing enzyme, was significantly reduced in PBMCs from T1DM patients. We confirmed that, compared to the control subjects, GLO1 expression and activity were markedly decreased and MG-derived AGEs were significantly accumulated in the PBMCs from T1DM patients. In addition, phytohemagglutinin stimulated the secretion of tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) was positively correlated with the accumulation of cellular AGEs. Therefore, the exposure of PBMCs from control subjects to MG and a GLO1 inhibitor enhanced the accumulation of cellular MG-derived AGEs and the secretion of TNF-α and IFN-γ.
CONCLUSIONS
The results of this study showed that the accumulation of cellular AGEs causes a decline in the immune response of patients with T1DM.
Topics: Humans; Diabetes Mellitus, Type 1; Leukocytes, Mononuclear; Tumor Necrosis Factor-alpha; Interferon-gamma; Glycation End Products, Advanced; Immunity
PubMed: 38420808
DOI: 10.31083/j.fbl2902085 -
Bulletin of Environmental Contamination... Feb 2024Industrial chemical contamination is known to have immuno-toxic effects on birds. It may also interfere with natural stressful conditions to further disrupt the immune...
Industrial chemical contamination is known to have immuno-toxic effects on birds. It may also interfere with natural stressful conditions to further disrupt the immune responses, but these possible interactive effects are still poorly documented in free-living birds. Using the phytohaemagglutinin skin-swelling test, we assessed how the T-cell mediated immune response varied according to the perceived risk of predation in hybrid sparrows, Passer domesticus × Passer hispaniolensis, originating from two sites differentially impacted by industrial chemical contamination, in southern Tunisia. Results showed that T-cell mediated immune response decreased with increasing perceived risk of predation, but the extent of this predator-associated immunosuppression was weaker in birds from the contaminated site compared to those from the control site. The immune response of birds living in the contaminated site was so weak that it could not be further weakened by a predator-related stress. Overall, these results support the idea that chemical contamination interferes with natural environmental stressors, such as predators, thus entailing profound disruption of the immune responses, with possible deleterious repercussions on the ability of birds to cope with diseases.
Topics: Animals; Sparrows; Industry; Tunisia; Predatory Behavior; Immunosuppression Therapy
PubMed: 38402343
DOI: 10.1007/s00128-024-03857-2 -
International Journal of Laboratory... Jun 2024
PubMed: 38837328
DOI: 10.1111/ijlh.14323