Biology subjects

Okuyama, H.

Publications and source records attributed to Okuyama, H..

4 recordsLinked to original sources

bioRxiv2025

Scaffold-free cryopreservable cartilage grafts obtained from hiPSC-derived chondroprogenitor cells for airway reconstruction with growth adaptability

Pediatric tracheal reconstruction remains a major clinical challenge because of limited graft availability and the need for growth-adaptive materials. Current approaches, such as costal cartilage grafting and use of scaffold-based constructs, often suffer from complications including graft resorption, donor site morbidity, and poor integration. Here, we present scaffold-free cartilage grafts (chondro-plates) derived from expandable limb-bud mesenchymal cells generated from human leukocyte antigen-homozygous human induced pluripotent stem cells. These grafts are cryopreservable and maintain their hyaline cartilage phenotype after a brief pre-culture. In both rat and rabbit tracheal defect models, chondro-plates supported robust cartilage regeneration, epithelial reconstitution, and neovascularization. Importantly, in a pediatric-like growing rat model, chondro-plates preserved luminal patency and structural integrity, outperforming autologous costal cartilage. This study demonstrates a clinically viable, off-the-shelf strategy for tracheal reconstruction using scalable, immunocompatible, and growth-adaptive cartilage grafts.

bioengineering↗

bioRxiv2025

Antigen-specific Th17 T cells offset the age-related decline in durable T cell immunity

Older adults are susceptible to infections, in part due to waning of immune memory. To determine mechanisms that determine long-lasting versus short-term immunity, we examined varicella zoster virus (VZV) vaccination as a model system. We contrasted VZV antigen-specific T cells several years after vaccination in adults who had been vaccinated at young (<20 years) or older age (>50 years) with a live-attenuated vaccine that confers durable protection only when given at young age, or with an adjuvanted VZV component vaccine that elicits effective, long-lasting immunity in older adults. CD8+ T cells were highly sensitive to age-related changes showing T cell subset shifts, loss in TCR diversity and reduced stem-like features while gaining NK-like signatures without evidence for cellular senescence or exhaustion. VZV-specific CD4+ T cells were largely resilient to age and maintained phenotypic and TCR diversity. Immunization of older adults with the adjuvanted VZV vaccine did not reverse age-associated defects in CD8+ T cells. Instead, it selectively improved the functionality of VZV-specific Th17 CD4+ T cells and prevented their acquisition of Treg features, likely as consequence of lipid metabolic pathways. Collectively, our data indicate that effective vaccination in older adults is supported by the generation of a durable, antigen-specific CD4+ Th17 population that resists mis-differentiation into Tregs and that compensates for age-related defects in CD8+ T cells. One sentence summaryAging primarily impairs the CD8+ T cell VZV vaccine response, while effective VZV vaccination in older adults induces antigen-specific Th17 CD4+ T cells to compensate for aging defects.

immunology↗

bioRxiv2025

Impact of Low-Dose Narrowband UV Radiation on Skin Tissue and Mast Cells in a Canine Model

Narrowband ultraviolet radiation (NB-UVR) therapy is widely utilized in dermatology worldwide. While the immunosuppressive effects of ultraviolet radiation are well-documented, its non-inflammatory effects remain poorly understood. This study evaluated the effects of sub-minimal erythema dose (MED) narrowband ultraviolet radiation using a canine model. The effects of narrowband-ultraviolet B (310 nm) and A2 wavelengths (320 and 330 nm) were compared. Initially, we demonstrated the therapeutic potential of NB-UVR in dogs with spontaneous atopic dermatitis (n = 6, p < 0.05). Following 300 mJ/cm{superscript 2} sub-MED ultraviolet radiation exposure, intradermal skin testing, skin mast cell counts, and RNA sequencing analysis were conducted. Additionally, cell viability (WST assay) and apoptosis (DAPI staining) were assessed in vitro using a canine mast cell line. Ultraviolet radiation exposure significantly reduced intradermal skin test scores across all wavelengths and decreased skin mast cell counts at 310 nm (n = 3, p < 0.05). In vitro, cell viability was significantly reduced at 310 and 320 nm (p < 0.05), and 310 nm irradiation specifically increased apoptotic cell numbers (p < 0.05). RNA sequencing identified 71 differentially expressed genes at 320 nm, with enrichment analysis highlighting muscle cell components and functions, potentially associated with arrector pili muscle activity. These findings suggest that 310 nm irradiation induces apoptosis, while 320 nm elicits non-inflammatory modulatory effects, highlighting distinct wavelength-specific therapeutic mechanisms of narrowband ultraviolet radiation.

immunology↗

bioRxiv2024

Aging trajectories of memory CD8+ T cells differ by their antigen specificity

Memory T cells are a highly dynamic and heterogeneous population that is maintained by cytokine-driven homeostatic proliferation interspersed with episodes of antigen-mediated expansion and contraction which affect their functional state and their durability. This heterogeneity complicates studies on the impact of aging on global human memory cells, specifically, it is unclear how aging drives memory T cell dysfunction. Here, we used chronic infection with Epstein-Barr virus (EBV) to assess the influence of age on memory states at the level of antigen-specific CD8+ T cells. We find that in young adults (<40 years), EBV-specific CD8+ T cells assume preferred differentiation states depending on their peptide specificity. By age >65-years, different T cell specificities had undergone largely distinct aging trajectories, which had in common a loss in adaptive and a gain in innate immunity signatures. No evidence was seen for cellular senescence or exhaustion. While naive/stem-like EBV-specific T cells disappeared with age, T cell diversity of EBV-specific memory cells did not change or even increased. In summary, by controlling for antigen specificity we uncover age-associated shifts in gene expression and TCR diversity that have implications for optimizing vaccination strategies and adoptive T cell therapy.

immunology↗