Molecular immunology最新文献

Baicalein is an active flavonoid compound derived from Scutellaria baicalensis, a member of the Lamiaceae family, and has been widely reported to exhibit antioxidant, anti-inflammatory, and antimicrobial properties. However, the precise mechanisms underlying the anti-inflammatory effects of baicalein in Toxoplasma gondii infection-induced inflammation remain unclear. This study aims to systematically investigate the regulatory effects of baicalein on inflammation associated with T. gondii infection and its molecular mechanisms. The results indicate that baicalein significantly inhibits T. gondii proliferation, the production of inflammatory mediators and reduces the expression levels of pro-inflammatory cytokines. Further experiments revealed that baicalein effectively blocks the excessive activation of the cGAS-STING and NOD-like receptor signaling pathways in T. gondii-stimulated Ana-1 cells, thereby inhibiting the amplification of inflammatory signals. Additionally, baicalein enhances the expression of autophagy-related proteins, promoting autophagy and alleviating oxidative stress-induced cellular damage and inflammation. In conclusion, this study demonstrates that baicalein exerts its anti-inflammatory effects by activating autophagy and inhibiting the excessive activation of cGAS-STING and NOD-like receptor signaling pathways, effectively suppressing T. gondii infection-induced macrophage inflammation. These findings provide new theoretical insights into the potential therapeutic application of baicalein in infectious diseases.

Atopic dermatitis is associated with higher risk for developing immune-related comorbidities, including other atopic diseases like food allergy as well as certain infections, autoimmune diseases, and cancers. It remains largely unknown whether this increased risk of comorbidities is attributable to underlying AD-induced changes in non-skin immune composition and function beyond the exacerbation of allergic immune responses. Here Brown Norway rats were sensitised to hydrolysed gluten though the skin in the absence or presence of AD-like skin inflammation induced by topical application of MC903. T cell phenotype composition was analysed in skin, blood, and gut tissues by flow cytometry. M1/M2 differentiation and cytokine production by intraperitoneal-derived macrophages stimulated with bacteria, inflammatory cytokines, or food allergens were analysed using flow cytometry and ELISA. Gut microbiota composition was analysed by partial 16S rRNA gene sequencing. Sensitisation in both the absence and presence of induced AD-like skin inflammation was found to predominantly affect T cell phenotype composition in skin and blood immune compartments. This systemic effect of AD had a minor effect on M1/M2 differentiation but did not affect cytokine production by intraperitoneal-derived macrophages. These findings highlight some systemic effects of skin sensitisation and AD that potentially could affect non-skin immune responses.

Ethnopharmacological relevance: Sophora tonkinensis radix et rhizoma is a medicinal herb traditionally used to treat inflammatory diseases and various types of cancer, previous phytochemistry studies have identified abundant alkaloids and flavonoids as the major bioactive components with anti-inflammatory, anti-tumor, hepatoprotective and immunomodulatory pharmacological effects, but their effects on Tumor-associated macrophages (TAMs) and the tumor immune microenvironment have not been systematically explored.

Aim of the study: This work aimed to establish whether a standardized extract of Sophora tonkinensis (STE) can halt IL-4-driven M2 macrophage polarization, reprogram established M2-like tumor-associated macrophages toward a pro-inflammatory M1-like phenotype, and clarify the underlying molecular mechanisms and in vivo efficacy of these immunomodulatory actions.

Materials and methods: Bone-marrow-derived macrophages (BMDMs) were polarized to an M2 phenotype and subsequently treated with STE. Expression of the M1/M2 markers Arg-1, CD206, iNOS, and CD86 in these macrophages was quantified by immunoblotting, qPCR, and flow cytometry. The impact of STE-pretreated M2-conditioned medium on the proliferation, migration, and invasion of Hepa 1-6 cells was then examined. H22 cells were subcutaneously inoculated into Balb/c mice to assess STE's effects on the macrophage landscape within the tumor immune microenvironment and to evaluate its antitumor efficacy.

Results: STE dose-dependently suppressed IL-4-induced Arg-1 and CD206 while up-regulating iNOS and CD86, indicating a blockade of M2 polarization and a shift toward an M1 signature. Mechanistically, STE markedly increased JAK1 and STAT1 phosphorylation. Functionally, it potently inhibited invasion and migration of Hepa 1-6 cells. In tumor-bearing mice, robust suppression of tumor growth was accompanied by a pronounced reduction in M2-like TAMs and a reciprocal increase in M1-like macrophages within the tumor microenvironment.

Conclusion: STE reprograms TAMs via the JAK1/STAT1 axis and exhibits robust antitumor activity, underscoring its promise as a natural, macrophage-targeted immunotherapeutic that warrants further investigation for integration into cancer treatment strategies.

Chronic myeloproliferative neoplasms (MPNs) are associated with dynamic and multifaceted changes in their immune microenvironment. Throughout disease progression, the interplay between pro-inflammatory ("yang") and immunosuppressive ("yin") cytokines and immune cells shapes the immune milieu and drives clinical progression. Sustained production of pro-inflammatory cytokines-such as interleukin-6 (IL-6) and interleukin-1β (IL-1β)-promotes clonal expansion and accelerates disease progression. Conversely, immunosuppressive mediators, including transforming growth factor-β (TGF-β) and interleukin-10 (IL-10), allow malignant clones to evade immune surveillance through the suppression of effector T-cell and natural killer (NK) cell cytotoxic functions. This dualistic immune state, with hyperactivation in early disease and immunosuppression in advanced stages, reflects the clinical and biological heterogeneity observed in MPNs. Emerging immunomodulatory therapies-such as interferon-α, Janus kinase (JAK) inhibitors, and other immunoregulatory agents-have demonstrated efficacy primarily by restoring immune balance. This review outlines the dual roles of immune cells and cytokines in MPN pathophysiology, emphasizes the significance of immune yin-yang imbalance, and evaluates current and prospective immunotherapeutic strategies for targeted immunologic intervention.

Background: Although the G2M checkpoint has been implicated in cancer metastasis in numerous studies, the genetic characteristics associated with the G2M checkpoint in Osteosarcoma (OS) remain unexplored.

Methods: Through univariate Cox regression analysis, we screened for G2M checkpoint-related genes associated with OS survival. The ConsensusClusterPlus R package was employed for clustering analysis of the TARGET-OS dataset. Finally, the immune infiltration, biological function, mutation and drug sensitivity of different clusters were analyzed. Furthermore, the functional mechanism of KIF20B was elucidated through in vitro experiments.

Results: The TARGET-OS cohort was clustered into two distinct clusters (Cluster 1 and Cluster 2). Compared to Cluster 2, Cluster 1 showed a trend towards higher overall survival rates, with higher immune scores, stromal scores, and ESTIMATE scores, alongside lower tumor purity. Additionally, the infiltration levels of immune cells were substantially higher in Cluster 1. In vitro experiments confirmed that overexpression of KIF20B promoted the proliferation and invasion of SOSP-9607 cells and induced G2/M phase arrest, upregulating the expression of core proteins in the G2/M pathway. Overexpression of KIF20B enhanced the sensitivity of cells to zoledronic acid, while the G2/M pathway inhibitor AZD-1775 reversed this effect.

Conclusion: This study elucidates the prognostic and immune microenvironmental characteristics of G2M checkpoint-related genes in OS, and validates the critical oncogenic function of KIF20B and its regulatory role in drug sensitivity. This study provides novel potential targets and strategies for molecular subtyping and targeted therapy of OS.