Biology subjects

Idoyaga, J.

Publications and source records attributed to Idoyaga, J..

3 recordsLinked to original sources

bioRxiv2025

Thymic DC2 are heterogenous and include a novel population of transitional dendritic cells

Myeloid cells, including dendritic cells (DCs) and macrophages, are essential for establishing central tolerance in the thymus by promoting T cell clonal deletion and regulatory T cell (Treg) generation. Previous studies suggest that the thymic DC pool consists of plasmacytoid DC (pDC), XCR1+ DC1 and SIRP+ DC2. Yet the precise origin, development, and homeostasis, particularly of DC2, remain unresolved. Using single-cell transcriptomics and lineage-defining mouse models we identify nine major populations of thymic myeloid cells and describe their lineage identities. What was previously considered to be "DC2" is actually composed of 4 distinct cell lineages. Amongst these are monocyte-derived DCs (moDC) and monocyte derived macrophages (moMac), which are dependent on thymic interferon to upregulate MHCII and CD11c. We further demonstrate that conventional DC2 undergo intrathymic maturation through CD40 signaling. Finally, amongst "DC2" we identify a novel thymic population of CX3CR1+ transitional DC (tDC), which represent transendothelial DCs positioned near thymic microvessels. Together, these finding reveal the thymus as a niche for diverse, developmentally distinct myeloid cells and elucidate their specific requirements for development and maturation.

immunology↗

bioRxiv2021

Injectable Nanoparticle-Based Hydrogels Enable the Safe and Effective Deployment of Immunostimulatory CD40 Agonist Antibodies

When properly deployed, the immune system can eliminate deadly pathogens, eradicate metastatic cancers, and provide long-lasting protection from diverse diseases. Unfortunately, realizing these remarkable capabilities is inherently risky as disruption to immune homeostasis can elicit dangerous complications or autoimmune disorders. While current research is continuously expanding the arsenal of potent immunotherapeutics, there is a technological gap when it comes to controlling when, where, and how long these drugs act on the body. Here, we explore the ability of a slow-releasing injectable hydrogel depot to reduce the problematic dose-limiting toxicities of immunostimulatory CD40 agonist (CD40a) while maintaining their potent anti-cancer efficacy. We leverage a previously described polymer-nanoparticle (PNP) hydrogel system that exhibits shear-thinning and yield-stress properties that we hypothesized would improve locoregional delivery of the CD40a immunotherapy. Using PET imaging, we demonstrate that prolonged hydrogel-based delivery redistributes CD40a exposure to the tumor and the tumor draining lymph node (TdLN), thereby reducing weight loss, hepatotoxicity, and cytokine storm associated with standard treatment. Moreover, CD40a-loaded hydrogels mediate improved local cytokine induction in the TdLN and improve treatment efficacy in the B16F10 melanoma model. PNP hydrogels, therefore, represent a facile, drug-agnostic method to ameliorate immune-related adverse effects and explore locoregional delivery of immunostimulatory drugs.

bioengineering↗

bioRxiv2020

Injectable hydrogels for sustained co-delivery of subunit vaccines enhance humoral immunity

Vaccines aim to elicit a robust, yet targeted, immune response. Failure of a vaccine to elicit such a response arises in part from inappropriate temporal control over antigen and adjuvant presentation to the immune system. In this work, we sought to exploit the immune systems natural response to extended pathogen exposure during infection by designing an easily administered slow-delivery vaccine platform. We utilized an injectable and self-healing polymer-nanoparticle (PNP) hydrogel platform to prolong the co-delivery of vaccine components to the immune system. We demonstrated that these hydrogels exhibit unique delivery characteristics whereby physicochemically distinct compounds (such as antigen and adjuvant) could be co-delivered over the course of weeks. When administered in mice, hydrogel-based sustained vaccine exposure enhanced the magnitude, duration, and quality of the humoral immune response compared to standard PBS bolus administration of the same model vaccine. We report that the creation of a local inflammatory niche within the hydrogel, coupled with sustained release of vaccine cargo, enhanced the magnitude and duration of germinal center responses in the lymph nodes. This strengthened germinal center response promoted greater antibody affinity maturation, resulting in a more than 1000-fold increase in antigen-specific antibody affinity in comparison to bolus immunization. In summary, this work introduces a simple and effective vaccine delivery platform that increases the potency and durability of subunit vaccines.

bioengineering↗