Biology subjects

Baleviciute, A.

Publications and source records attributed to Baleviciute, A..

3 recordsLinked to original sources

bioRxiv2026

CD11c+ microglia promote dysfunctional T cell activation in diffuse midline glioma

Paediatric diffuse midline glioma (DMG) remains refractory to immunotherapy despite T-cell infiltration, indicating that local mechanisms actively suppress anti-tumour immunity. Using complementary genetic and orthotopic mouse models, we performed lineage-resolved profiling of the DMG immune microenvironment, resolving myeloid ontogeny and microglial states by distinguishing resident microglia from infiltrating bone marrow-derived macrophages. We identified microglia as the predominant tumour-associated myeloid population and discovered selective expansion of CD11c positive; microglia exhibiting enriched antigen-presentation and immune-regulatory transcriptional programs. Tumour-infiltrating CD4+; and CD8+; T cells exhibited chronic activation and exhaustion, while ligand receptor analysis predicted inhibitory microglia T cell communication. Pharmacological CSF1R inhibition depleted CD11c positive; microglia, attenuated antigen-presentation and immune-regulatory programs, and shifted tumour-infiltrating T cells toward a less exhausted phenotype. Together, these findings identify a previously unrecognised CD11 positive; microglia T-cell axis that establishes immune dysfunction in DMG and provide a rationale for combining myeloid- and T cell-targeted immunotherapies.

cell biology↗

bioRxiv2026

Microbiota-sensitive glial and metabolic programs define a critical window in early postnatal brainstem development

Paediatric brain tumours are increasingly recognised as diseases of disrupted development, arising when lineage progression programs, that normally govern neural and glial maturation, become stalled or dysregulated. Diffuse midline glioma (DMG), a highly aggressive paediatric brainstem tumour, emerges during early childhood in the pons, a region undergoing rapid postnatal growth characterized by oligodendrocyte precursor cell (OPC) proliferation and differentiation. However, the environmental factors that shape these developmental trajectories remain poorly defined. Here, using germ-free and conventionally colonized mice, we investigated whether early-life microbiota influences transcriptional and metabolic programs in the developing brainstem during this critical developmental window. Bulk RNA sequencing revealed pronounced microbiota-associated transcriptional differences at postnatal day 2 (P2), but not at P8, identifying a temporally restricted period during which microbial colonization is associated with pathways linked to oligodendrocyte lineage progression, myelination, and neuroimmune signalling. Transcriptional analyses further identified altered expression of genes associated with CD11c microglia, a developmental microglial subtype implicated in regulating oligodendrocyte maturation. Untargeted metabolomic profiling revealed parallel microbiota-associated differences in pathways related to mitochondrial function, redox balance, and methyl-donor metabolism. Integrated multi-omics analyses identified coordinated networks linking glial lineage programs with metabolites involved in cellular metabolism and epigenetic regulation. Notably, several of these transcriptional and metabolic programs overlap with gene signatures reported in diffuse midline glioma, suggesting that microbiota-sensitive developmental pathways intersect with cellular states relevant to paediatric brainstem tumour biology.

neuroscience↗

bioRxiv2023

Understanding the Immunomodulatory Effects of Bovine Colostrum: Insights into IL-6/IL-10 Axis-Mediated Inflammatory Control

Bovine colostrum (COL), the first milk secreted by lactating cows postpartum, is a rich source of bioactive compounds that exert significant role on the survival, growth, and immune development of neonatal calves [9,10]. This study investigated the immunomodulatory effects of COL on cytokine production in vitro using a Caco-2/THP-1 macrophage co-culture model stimulated with Phorbol 12-myristate 13-acetate (PMA). COL pretreatment significantly reduced IL-6 production induced by PMA, while increasing IL-10 production. Further investigations revealed that the IL-6 suppressive effect of colostrum was heat-sensitive and associated with components of higher molecular mass (100 kDa). Moreover, colostrum primarily influenced THP-1 macrophages rather than Caco-2 epithelial cells. The effects of colostrum on IL-6 production were associated with reduced NF-{kappa}B activation in THP-1 macrophages. In calf-FMT transplanted C57BL/6 murine model, colostrum decreased intestinal permeability, reduced immune cell infiltration, and suppressed IL-6 production during S. typhimurium infection. These results highlight the immunomodulatory activity of bovine colostrum and its potential therapeutic applications in inflammatory disorders. Further studies are needed to elucidate the underlying mechanisms and validate the findings in bovine models. Simple SummaryThis study explores the immunomodulatory properties of bovine colostrum (COL), the initial milk produced by lactating cows, on cytokine production in vitro and in a novel murine calf-FMT model. The researchers utilized a Caco-2/THP-1 macrophage co-culture model stimulated with Phorbol 12-myristate 13-acetate (PMA) to investigate the effects of COL on cytokine production. The findings indicate that COL pretreatment significantly reduced IL-6 production while enhancing IL-10 production. The IL-6 suppressive effect was heat-sensitive and associated with components of higher molecular mass (100 kDa). Colostrum demonstrated decreased intestinal permeability, reduced immune cell infiltration, and suppressed IL-6 production during S. typhimurium infection. These results highlight the immunomodulatory potential of bovine colostrum and its prospective therapeutic applications in inflammatory disorders. Further research is necessary to elucidate the underlying mechanisms and corroborate the findings in bovine models.

immunology↗