Immunological Investigations最新文献

Introduction: Human oral squamous cell carcinoma (OSCC) is the most common type of oral cancer and has a poor survival rate. Cell-cell communication between OSCC cells and cancer-associated fibroblasts (CAFs) plays important roles in OSCC progression. We previously demonstrated that CAFs promote OSCC cell migration and invasion. However, how OSCC cells influence CAFs proliferation is unknown.

Methods: Knockdown of PVT1 was confirmed using lentivirus infection technique. CAFs in tissues were identified by staining the cells with α-SMA using immunohistochemical technique. CCK-8 assay was used to evaluate cell proliferation. The mRNA level of a gene was measured by qRT-PCR. Secreted TGF-β were detected using ELISA assay.

Results: We found that knockdown of the long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) was associated with a low density of CAFs in xenograft tumors in mice; further analysis revealed that PVT1 in OSCC cells induced CAF proliferation through transforming growth factor (TGF)-β.

Discussion: Our results demonstrate that lncRNA PVT1 in tumor cells participates in CAF development in OSCC by regulating TGF-β. This study revealed a new mechanism by which PVT1 regulates OSCC progression and PVT1 is a potential therapeutic target in OSCC.

Background: The incidence of osteoarthritis (OA) is increasing, yet its pathogenesis remains largely unknown. Recent studies suggest that abnormal subchondral bone remodeling plays a crucial role in OA development, highlighting a gap in clinical treatments targeting this aspect. Soybean Isoflavone (SI) has shown potential in treating OA, although its mechanisms are not fully understood.

Methods: This research investigated the effects of SI on subchondral bone remodeling in an OA rat model, assessing joint damage, OARSI scores, and type H vessel formation (CD31hiEmcnhi expression). Additionally, the expression of ALP, OCN, BMP, and TSC1 was evaluated to determine involvement of the mTORC1 pathway. In vitro studies on IL-1β-induced osteoblasts further examined the impact of SI on TSC1/mTORC1 signaling and related markers.

Results: SI treatment reduced joint damage and OARSI scores in the rat OA model, significantly decreasing CD31hiEmcnhi expression, indicating a reduction in type H vessel formation. SI also downregulated ALP, OCN, and BMP expression while upregulating TSC1, suggesting inhibition of the mTORC1 signaling pathway and VEGF release. In vitro, SI increased TSC1 expression and decreased mTORC1 signaling, VEGF, ALP, OCN, and BMP levels in IL-1β-induced osteoblasts.

Conclusion: SI targets the TSC1/mTORC1 signaling pathway to suppress osteoblast activation and VEGF release, inhibiting type H vessel formation and slowing abnormal subchondral bone remodeling. These findings provide a novel therapeutic approach for OA by focusing on subchondral bone remodeling mechanisms.

Introduction: One-lung ventilation (OLV) is a prevalently used technique to sustain intraoperative pulmonary function. Resolvin E1 (RvE1), a specialized pro-resolving lipid mediator, accelerates the resolution of inflammation in the lungs. However, its therapeutic effects on OLV-induced lung injury remain unclear.

Methods: We initially developed an OLV rat model and treated it with RvE1. Subsequently, we assessed the wet/dry ratio of the lung tissue, performed hematoxylin and eosin staining, and calculated the ratio of polymorphonuclear cells to white blood cells in the bronchoalveolar lavage fluid. Additionally, we assessed apoptosis, inflammatory factor levels, and lung permeability in the rat lung tissues in the RvE1 treated and untreated groups and explored the molecular mechanisms mediated by RvE1.

Results: Our results indicated that RvE1 alleviated lung injury and inflammation and improved lung tissue apoptosis and permeability in OLV rats. Moreover, RvE1 suppressed the expression of the BLT1/2 signaling pathway and its ligands. The use of BLT2 and BLT1 inhibitors (LY255283 and U-75302, respectively) enhanced RvE1's anti-inflammatory effects and reduced lung injury. Furthermore, synergistic treatment with the BLT2 inhibitor and RvE1 provided grater benefits by more effectively inhibiting the NF-kB, p38 MAPK, and ERK pathways.

Discussion: RvE1 and the inhibition of BLT2 signalling reduce the inflammatory response and mitigate OLV-induced lung injury. These findings suggest a novel therapeutic pathway for managing OLV-related complications.

Objective: This study was performed to explore the clinical significance of the expression of human beta-defensin 2 (HBD-2) and chemokine ligand 1/2 (CXCL-1/2) in psoriasis vulgaris.

Methods: This study retrospectively included the study group (n = 160) and control group (n = 100) for analysis. The levels of inflammatory indicators, blood biochemical indicators, and immune indicators using ELISA. The psoriasis area and severity index (PASI) was used to evaluate disease severity. Levels of HBD-2, CXCL-1, CXCL-2 and CCL20 were determined by RT-PCR. The correlations of HBD-2, CXCL-1 and CXCL-2 levels with CCL20 and PASI scores were analyzed. The diagnostic value of HBD-2, CXCL-1 and CXCL-2 in psoriasis vulgaris was analyzed by ROC curve.

Results: HBD-2, CXCL-1 and CXCL-2 were highly expressed in the lesions of psoriasis vulgaris patients, and were positively correlated with CCL20 and PASI score. HBD-2, CXCL-1 and CXCL-2 alone or in combination had high diagnostic value for psoriasis vulgaris and severe psoriasis, and the combined diagnostic value of the three was higher than that of a single indicator.

Conclusion: HBD-2, CXCL-1, and CXCL-2 levels are closely related to the severity of psoriasis vulgaris and can effectively diagnose the occurrence and progression of psoriasis vulgaris.

Introduction: This study aimed to elucidate the functional genes associated with systemic lupus erythematosus (SLE) in various cell types through the utilization of RNAm-SNPs.

Methods: Utilizing large-scale genetic data, we identified associations between RNAm-SNPs and SLE. The association between RNAm-SNPs and bulk and single-cell mRNA expression (eQTL) and protein levels (pQTL) were examined. Mendelian randomization and differential expression analyses were conducted to explore the links between gene expression, protein levels, and SLE.

Results: We identified 41 RNAm-SNPs that were significantly associated with SLE. The GWAS signals exhibited notable enrichment in m⁶A-SNPs and m⁷G-SNPs. These RNAm-SNPs showed both eQTL and pQTL effects. In our single-cell analysis, 16 RNAm-SNPs exhibited associations with gene expression levels across 13 distinct cell types, including HLA-A, HLA-B, HLA-C, HLA-DQA1, HLA-DQB1, HLA-DRB1 and IRF7. We identified 58 noteworthy associations between the expression levels of 20 genes and SLE across 12 distinct immune cell types. Notably, HLA-DQB1, HLA-DRB1 and IRF7 exhibited abnormalities in CD8+ T cells, IRF7 displayed abnormal expression in CD4+ T cells, while HLA-DRB1 and IRF7 were also distinctly perturbed in natural killer cells.

Discussion: This study advances our understanding of the genetic basis of SLE by highlighting the significance of RNAm-SNPs and immune cell gene expression in SLE.

Background: TANK-binding kinase 1 (TBK1) is a pivotal mediator of innate immunity, activated by receptors such as mitochondrial antiviral signaling protein (MAVS), stimulator of interferon genes (STING), and TIR-domain-containing adaptor inducing interferon-β (TRIF). It modulates immune responses by exerting influence on the type I interferons (IFN-Is) signaling and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways, Over the past few years, TBK1 multifaceted role in both immune and inflammatory responses is increasingly recognized.

Methods and results: This review aims to scrutinize how TBK1 operates within the NF-κB pathway and the interferon regulatory transcription factor 3 (IRF3)-dependent IFN-I pathways, highlighting the kinases and other molecules involved in these processes. This analysis reveals the distinctive characteristics of TBK1's involvement in these pathways. Furthermore, it has been observed that the role of TBK1 in exerting anti-inflammatory or pro-inflammatory effects is contingent upon varying pathological conditions, indicating a multifaceted role in immune regulation.

Discussion: TBK1's evolving role in various diseases and the potential of TBK1 inhibitors as therapeutic agents are explored. Targeting TBK1 may provide new strategies for treating inflammatory disorders and autoimmune diseases associated with IFN-Is, warranting further investigation.

Background: Allergic asthma is characterized by airway hyperresponsiveness triggered by inhaled allergens. Type 2 innate lymphoid cells (ILC2s) have been demonstrated to play a crucial role in promoting airway inflammation through the secretion of type 2 effector cytokines. However, the mechanisms underlying the functions of lung ILC2s remain unclear.

Methods: In this study, we investigated the expression of IRF3 in ILC2s in both human patients and mouse models of asthma. We utilized IRF3-deficient mice to assess the impact of IRF3 deficiency on ILC2 function in a model of IL33-induced asthma. Additionally, we explored the mechanisms underlying IRF3-mediated regulation of ILC2s, focusing on the involvement of the transcription factor Gata3.

Results: Our findings revealed elevated expression of IRF3 in ILC2s of patients and mice with asthma, suggesting a potential role for IRF3 in the pathogenesis of allergic asthma. Furthermore, we demonstrated that IRF3 deficiency impairedthe expansion and function of ILC2s in IL33-induced asthma, highlighting the importance of IRF3 in regulating ILC2-mediated responses. Importantly, we showed that the regulation of ILC2s by IRF3 was independent of Th2 cells and mediated by the transcription factor Gata3.

Conclusion: This study identifies IRF3 as a novel regulator of lung ILC2s and suggests its potential as a promising immunotherapeutic target for allergic asthma. These findings shed light on the intricate mechanisms underlying asthma pathogenesis and provide insights into potential strategies for the development of targeted therapies for this prevalent airway disease.

Background: Tectochrysin suppresses several diseases. In this study, we aimed to explore the effects of tectochrysin ona rat model of periodontitis PDS).

Methods: Male Sprague-Dawley (SD) rats were subjected to ligature to induce periodontitis. Bone parameters were analyzed using micro-computed tomography and periodontal tissues were evaluated using Masson's, hematoxylin and eosin, and tartrate-resistant acid phosphatase staining. The expression of HO-1, Nrf2, CD206, Arg-1, and iNOS was evaluated using immunohistochemistry. Malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD) levels and IL-1β, IL-6, and tumor necrosis factor (TNF)-α,and NF-κB and Nrf2/HO-1 were analyzed.

Results: Tectochrysin reduced alveolar bone loss, promoted new bone formation, and inhibited osteoclast formation in periodontitis rats. It decreased the number of inflammatory cells and the levels of IL-1β, IL-6, and TNF-α, indicating a reduction in inflammation. Tectochrysin restored the Arg-1/iNOS ratio, indicating M2 macrophage polarization, and inhibited the NF-kB pathway. Tectochrysin restored GSH and SOD levels, inhibited MDA content, and activated the HO-1/Nrf2 pathway.

Conclusion: Tectochrysin alleviates PDS in rats by modulating the M2/M1 macrophage ratio via the NF-kB pathway and suppressing oxidative stress via the HO-1/Nrf2 pathway.

Background: Immunotherapy is an emerging strategy in cancer therapeutics aimed at modulating the immune system to inhibit pro-tumor pathways and increase a tumor's sensitivity to chemotherapy. Several clinically approved immunotherapy treatments, such as monoclonal antibody treatments, have been successful in solid tumors such as breast, colorectal, and pancreatic. However, an outstanding challenge of these strategies is tumor cell resistance. One target of interest for immune cell modulation is targeting macrophages that enter the tumor microenvironment. More specifically, an immune checkpoint of interest is CD47. CD47 is a transmembrane protein that inhibits phagocytic activity by acting as a "don't eat me" signal. In both mice and humans, healthy cells can express CD47, while solid malignancies like colorectal and breast cancer express it most strongly.

Methods: Analysis of literature data on the physiological and functional roles of tissue-resident macrophages, along with the structure and mechanisms of action of the CD47 pathway was explored. We also explored how CD47 can influence different aspects of the tumor microenvironment (i.e. cellular metabolism and hypoxia) in addition to current clinical strategies and challenges associated with targeting CD47.

Results: Overall, it was discovered that CD47 is overexpressed in a variety of cancer types in addition to normal tissue, making it a promising treatment regimen to enhance the capability of macrophages to phagocytose tumor cells. However, treatment efficacy is varied in pre-clinical and clinical models due to various challenges such as off-target effects.

Conclusion: This review emphasizes the diverse functionality of macrophages in normal and cancerous tissue, while also emphasizing the importance of macrophage targeting and their clinical significance.

Background: Colorectal cancer (CRC) is the most common malignancy of the digestive system in the world. Immune cells and molecules in tumor microenvironment are crucial.Identifying immune system components in cancer aids in biomarker discovery. This study investigated the serum IgE levels and expression of IL-4 and IL-13 in the tissue and serum of CRC patients and explored their possible association with pathological and clinical factors.

Materials and methods: Thirty-six patients with CRC and 36 healthy individuals were involved in the study. Tissues and blood samples were collected. Serum levels of IgE and IL-4 and IL-13 were analyzed using the ELISA method. The quantitative Real-Time PCR (qRT-PCR) technique was used to assess the expression levels of the cytokines in CRC tissue samples in comparison with the adjacent control tissue.

Results: Our results revealed that the serum level of IL-4 and IL-13 and also their gene expression levels were significantly decreased in CRC patients compared to the controls. The results of this study revealed that there is no significant difference in the serum levels of IgE between CRC patients and the control group.

Conclusion: All in all, the results of the current research suggest that the expression levels of IL-13, IL-4, and IgE vary between CRC tissue.