Biology subjects

Vuong, I.

Publications and source records attributed to Vuong, I..

3 recordsLinked to original sources

bioRxiv2026

Serum albumin-fused interleukin-10 prevents neuroinflammation by promoting immunoregulation in the secondary lymphoid organs and limiting immune cell infiltration in the spinal cord

Interleukin-10 (IL-10) is a potent immunoregulatory cytokine that suppresses pro-inflammatory cytokine production, reduces antigen presentation by myeloid cells, promotes M2 macrophage polarization, and inhibits T cell activation. Despite these well-established immunoregulatory functions, efforts to harness recombinant IL-10 therapeutically have been limited by its short plasma half-life and poor retention in the secondary lymphoid organs (SLOs), key sites of autoreactive T cell priming in autoimmune disease. Previously, we engineered a fusion of serum albumin and IL-10 (SA-IL-10) with extended half-life and enhanced exposure in the SLOs following intravenous administration. Here, we integrate human transcriptomic analyses and a murine model of neuroinflammation, experimental autoimmune encephalomyelitis (EAE), to investigate how sustained IL-10 exposure in the SLOs modulates immune responses under inflammatory conditions. Human single-cell RNA sequencing analyses revealed reduced IL-10 expression alongside increased IL-10 receptor expression across multiple immune cell populations in treatment-naive patients with multiple sclerosis (MS), motivating the investigation of IL-10-based immunomodulatory strategies. Prophylactic SA-IL-10 administration prevented the development and progression of EAE with superior efficacy to wild type IL-10 and comparable protection to fingolimod, an FDA-approved MS therapy. Immunophenotyping of the SLOs revealed that SA-IL-10 suppressed pathogenic, antigen-specific ROR{gamma}t+ Foxp3- TH17 T cells, CD86+ M1-like macrophages, CD86+ dendritic cells, and pro-inflammatory cytokine production, while expanding immunoregulatory CD206+ M2-like macrophages and increasing the frequency of multiple checkpoint markers (CTLA-4, PD-1, TIGIT, ICOS) on GATA3+ Foxp3- TH2 cells. Despite the absence of direct central nervous system targeting, SA-IL-10 treatment also reduced the infiltration of macrophages, dendritic cells, and CD4+ T cells into the spinal cord. Repeated SA-IL-10 administration was well tolerated, as treated EAE mice gained significantly more body weight over the course of treatment compared to PBS- and WT IL-10-treated controls, and exhibited plasma biochemistry parameters comparable to control animals at study endpoint. Together, these findings demonstrate that increasing IL-10 exposure in the SLOs suppresses neuroinflammation by promoting immunoregulation.

immunology↗

bioRxiv2025

mRNA lipid nanoparticle-incorporated nanofiber-hydrogel composite generates a local immunostimulatory niche for cancer immunotherapy

Hydrogel materials have emerged as versatile platforms for various biomedical applications. Notably, the engineered nanofiber-hydrogel composite (NHC) has proven effective in mimicking the soft tissue extracellular matrix, facilitating substantial recruitment of host immune cells and the formation of a local immunostimulatory microenvironment. Leveraging this feature, here we report an mRNA lipid nanoparticle (LNP)-incorporated NHC microgel matrix, termed LiNx, by incorporating LNPs loaded with mRNA encoding tumour antigens. Harnessing the potent transfection efficiency of LNPs in antigen-presenting cells (APCs), LiNx demonstrates remarkable immune cell recruitment, antigen expression and presentation, and cellular interaction. These attributes collectively create an immunostimulating milieu and yield a potent immune response achievable with a single dose, comparable to the conventional three-dose LNP immunization regimen. Further investigations reveal that the LiNx not only generates heightened Th1 and Th2 responses but also elicits a distinctive Type 17 T helper cell-mediated response pivotal for bolstering antitumour efficacy. Our findings elucidate the mechanism underlying LiNxs role in potentiating antigen-specific immune responses, presenting a new strategy for cancer immunotherapy.

bioengineering↗

bioRxiv2020

Singleton phage BlueFeather reveals novel relationships in the Arthrobacter phage population

Bacteriophages (phages) exhibit high genetic diversity, and the mosaic nature of the shared genetic pool makes quantifying phage relatedness a shifting target. Early parameters for clustering of related Mycobacteria and Arthrobacter phage genomes relied on nucleotide identity thresholds but, more recently, clustering of Gordonia and Microbacterium phages has been performed according to shared gene content. Singleton phages lack the nucleotide identity and/or shared gene content required for clustering newly sequenced genomes with known phages. Whole genome metrics of novel Arthrobacter phage BlueFeather, originally designated a putative singleton, showed low nucleotide identity but high amino acid and gene content similarity with Arthrobacter phages originally assigned to Clusters FE and FI. Gene content similarity revealed that BlueFeather shared genes with these phages in excess of the parameter for clustering Gordonia and Microbacterium phages. Single gene analyses revealed evidence of horizontal gene transfer between BlueFeather and phages in unique clusters that infect a variety of bacterial hosts. Our findings highlight the advantage of using shared gene content to study seemingly genetically isolated phages and have resulted in the reclustering of BlueFeather, a putative singleton, as well as former Cluster FI phages, into a newly expanded Cluster FE.

microbiology↗