Cytokine Signature and Involvement in Chronic Rhinosinusitis with Nasal Polyps

Cytokines are well known to play a central role in chronic rhinosinusitis with nasal polyps (CRSwNP), particularly in maintenance of the inflammatory response and the recruitment of eosinophils. The pathophysiological concepts concerning the involvement of inflammatory cytokines in CRSwNP have gradually evolved. Although the Th2 cytokines environment associated with an eosinophilic infiltration has retained a central role in the genesis of polyps, the role of other cytokine subpopulations has also and more recently been detailed, leading to a specific and complex signature in CRSwNP. The purpose of this review is to summarize the current state of knowledge about the cytokine signature in CRSwNP, the role of cytokines in the pathogenesis of this disease and in the intercellular dialog between epithelial cells, fibroblasts and inflammatory cells. Knowledge of this precise cytokine signature in CRSwNP is fundamental in the perspective of potential targeting biotherapies.

Macrophage immunomodulatory activity of Acanthopanax senticousus polysaccharide nanoemulsion via activation of P65/JNK/ikkαsignaling pathway and regulation of Th1/Th2 Cytokines

Nanoemulsions (NE) are used widely in pharmaceutical drug formulations and vaccine preparation, and Acanthopanax senticousus polysaccharide (ASPS) is a natural bioactive compound with immunostimulatory activity. Therefore, NE-loaded ASPS is expected to provide immunological enhancement for effective treatment. In the present study, Acanthopanax senticousus polysaccharide (ASPS was encapsulated into nanoemulsions, the resultant ASPS–NE were coated with a negative charge, and the immune enhancement mechanism of these ASPS-NE formulations was analyzed. The immunosuppressive animal models (70 ICR mice, male) for the study were established using cyclophosphamide. In addition, the activation of splenocyte proliferation, phagocytosis of the macrophages, the ratio of CD4+ to CD8+, the concentrations of the cytokines in serum, Western blot analysis was used for the analysis of the P65/JNK/ikk α signaling pathway in the peritoneal macrophage s. The results revealed that the ASPS-NE could stimulated the proliferation of splenocytes and enhance immunity. The ASPS-NE induced the expression of different cytokines (TNF-α, IFN-γ, IL-2, and IL-6), could activate the expressions of P65, JNK, and ikkα, and regulated the Th1/Th2 cytokines. These findings demonstrated the potential of ASPS-NE formulations for drug delivery and to induce potent and sustained immune responses.

Tumor-B-cell Interactions Promote Isotype Switching to an Immunosuppressive IgG4 Antibody Response Through Upregulation of IL-10 in Triple Negative Breast Cancers

BackgroundTriple negative breast cancer (TNBC) is an aggressive breast cancer for which there is currently no targeted therapy. Tumor-infiltrating B-cells (TIB) have been observed in tumor tissues of TNBC patients, but their functional role is unclear. IgG4 is one of four antibody subclasses of IgG expressed and secreted by B cells. Unlike other IgG isotypes, IgG4 has an immunosuppressive function and is induced by Th2-type cytokines. In cancers such as melanoma, IgG4 has been linked with advanced disease and poor patient survival. Therefore, we sought to determine the role of IgG4 in TNBC. MethodsWe performed co-culture assays to examine expression of Th2 cytokines by TNBC cells with and without the presence of B cells. We also performed in vitro class switching experiments with peripheral B cells with and without co-culture with TNBC cells in the presence or absence of an IL-10 blocking antibody. We examined expression of CD20 + TIB, IgG4 and Th2 cytokines by immunohistochemistry in 152 TNBC samples. Statistical analysis was done using Log-Rank and Cox-proportional hazards tests. ResultsOur findings indicate that B cells interact with TNBC to drive chronic inflammatory responses through increased expression of inflammatory cytokines including the TH2 cytokines IL-4 and IL-10. In vitro class switching studies show that interactions between TNBC cell lines and B cells drive isotype switching to the IgG4 isotype in an IL-10 dependent manner. In patient tissues, expression of IgG4 correlates with CD20 and tumor expression of IL-10. Both IgG4 and tumor IL-10 are associated to shorter recurrence free survival (RFS) and overall survival (OS) in TNBC. In a multi-variant analysis, IL-10 was associated with poor outcomes indicating that tumor IL-10 may drive immune escape. ConclusionsThese findings indicate that interactions between TIB and TNBC results in activation of chronic inflammatory signals that suppress antibody driven immune responses

Th1/Th2 Cytokine Profiles Differentiating Tuberculous from Malignant Pleural Effusions: A Systematic Review and Meta-Analysis

To clarify which one has a different predominance of Th1 and Th2 immune responses in malignant and tuberculous pleural effusions. We did a meta-analysis of the results published previously to assess the levels of Th1/Th2 cytokines in two types of pleural effusion, and evaluated its ability to distinguish TPE from MPE. We queried the PubMed and Embase databases for studies indexed from 2000 up to March 2021. We included studies that (a) diagnosis of TPE and MPE by on culture, or pleural biopsy tissue provided; (b) compared levels of Th1/Th2 cytokines in pleural effusion between TPE and MPE. Pooled data by using a random-effects model or fixed-effects model, standardized mean differences (SMD) across studies comparing TPE and MPE. We also performed Egger test to assess of publication bias. Of 917 identified studies, a total of 42 studies were selected in the meta-analysis. Compared with malignant subjects, tuberculous subjects had a significant higher level of TNF-α [2.22, (1.60–2.84)], an elevated level of IFN-γ [3.30, (2.57–4.40)] in pleural effusion, a situation where the Th1 immune response dominates. Conversely, Interleukin-4 (IL-4) and IL-10 (Th2 cytokines) levels were higher in MPE than TPE. Besides, they were shown to be statistically insignificant tiny effects were [-0.15, (-0.94–0.63)], [-0.04, (-0.21–0.12)] respectively. We confirmed that pleural effusions caused by tuberculosis, a situation in which the Th1 cytokines are predominant. The slight preponderance of Th2 cytokines in malignant pleural effusions, which are not convincing enough to prove.