Biology subjects

Vecchio, F.

Publications and source records attributed to Vecchio, F..

5 recordsLinked to original sources

bioRxiv2026

Coxsackievirus B Escapes Antiviral CD8⁺ T Cells but Triggers Robust CD4⁺ Memory Responses

Coxsackieviruses B (CVBs) are plausible triggers of the pancreatic islet autoimmunity leading to type 1 diabetes. Islet autoantibody seroconversion correlates with persistent CVB infections in the gut and pancreas, suggesting defective antiviral control and the need to define immune mechanisms at the intestinal entry site. We investigated how CVB3 modulates antigen presentation, the viral immunopeptidome of enterocytes and antigen-presenting cells, and downstream T-cell immunity. CVB3-infected enterocytes escaped immune recognition by downregulating HLA Class I and viral peptide presentation, impairing CD8+ T-cell responses in vitro. In CVB-seropositive individuals, circulating CVB-reactive CD8+ T cells were stalled in naive-like and exhausted effector/memory states. In contrast, CVB3 induced HLA class II upregulation, promoting robust CD4 T-cell activation. Circulating CVB3-reactive CD4 T cells fully differentiated into polyfunctional T helper memory. These findings indicate that CVB3 antiviral control is predominantly CD4 T-cell-mediated and provide a rationale for mucosal vaccination strategies and immune monitoring tools to follow infection or vaccination. TeaserCoxsackievirus evades CD8+ T-cell immunity in the gut, leaving CD4+ T cells as the main line of antiviral defense.

immunology↗

bioRxiv2025

Uniaxial tensile tests and Digital Image Correlation analysis for the mechanical characterization of human Fascia Lata under different decellularization treatments

Fascia Lata (FL) is frequently employed as a graft source in reconstructive surgery. To minimize unwanted responses from the host immune system, several decellularization treatments have been proposed. Effective treatments should aim at avoiding the deterioration of the physical and mechanical properties of the implanted tissue. In this work, we carried out a mechanical characterization of FL specimens from human dead donors, both in their native-physiological condition and upon decellularization with three commonly used detergents, t-octyl-phenoxypolyethoxyethanol (Triton X-100), sodium dodecyl sulfate (SDS), and tri-n-butyl phosphate (TnBP). Uniaxial tensile tests were used to characterize the elastic stiffness and ultimate stresses of the tissue, and Digital Image Correlation (DIC) was applied to monitor the strain evolutions and meso-mechanical deformation responses. None of the investigated decellularization protocols was found to lead to a significant deterioration of the FL mechanical properties, suggesting the applicability of these chemical treatments for graft preparation and usage in the clinical practice. The application of DIC also allowed us to get a first estimate of the FL Poisson ratio as well as to draw the attention on the inhomogeneity of strain distributions, suggesting that the use of average engineering strains can lead to an oversimplification of the actual deformation field.

bioengineering↗

bioRxiv2023

Cortical spheroids show strain-dependent cell viability loss and neurite disruption following sustained compression injury

Sustained compressive injury (SCI) in the brain is observed in numerous injury and pathological scenarios, including tumors, ischemic stroke, and traumatic brain injury-related tissue swelling. Sustained compressive injury is characterized by tissue loading over time, and currently, there are few in vitro models suitable to study neural cell responses to strain-dependent sustained compressive injury. Here, we present an in vitro model of sustained compressive neural injury via centrifugation. Spheroids were made from neonatal rat cortical cells seeded at 4000 cells/spheroid and cultured for 14 days in vitro. A subset of spheroids was centrifuged at 209 or 419 rad/s for 2 minutes. Modeling the physical compression of the spheroids via finite element analyses, we found that spheroids centrifuged at 209 and 419 rad/s experienced pressures of 38 kPa and 149 kPa, respectively, and compressive strains of 18% and 35%, respectively. Quantification of LIVE-DEAD assay and Hoechst 33342 nuclear staining showed that centrifuged spheroids exhibited significantly higher DNA damage than control spheroids at 2, 8, and 24 hours post-injury. Immunohistochemistry of {beta}3-tubulin networks at 2, 8, and 24 hours post-centrifugation injury showed increasing degradation of microtubules over time with increasing compressive strain. Our findings show that cellular injuries occur as a result of specific levels and timings of sustained compressive tissue strains. This experimental compressive injury model provides an in vitro platform to examine cellular injury to gain insights into brain injury that could be targeted with therapeutic strategies.

bioengineering↗

bioRxiv2023

Coxsackievirus infection induces direct pancreatic β-cell killing but poor anti-viral CD8+ T-cell responses

Coxsackievirus B (CVB) infection of pancreatic {beta} cells is associated with {beta}-cell autoimmunity. We investigated how CVB impacts human {beta} cells and anti-CVB T-cell responses. {beta} cells were efficiently infected by CVB in vitro, downregulated HLA Class I and presented few, selected HLA-bound viral peptides. Circulating CD8+ T cells from CVB-seropositive individuals recognized only a fraction of these peptides, and only another sub-fraction was targeted by effector/memory T cells that expressed the exhaustion marker PD-1. T cells recognizing a CVB epitope cross-reacted with the {beta}-cell antigen GAD. Infected {beta} cells, which formed filopodia to propagate infection, were more efficiently killed by CVB than by CVB-reactive T cells. Thus, our in-vitro and ex-vivo data highlight limited T-cell responses to CVB, supporting the rationale for CVB vaccination trials for type 1 diabetes prevention. CD8+ T cells recognizing structural and non-structural CVB epitopes provide biomarkers to differentially follow response to infection and vaccination.

immunology↗

bioRxiv2022

The type 1 diabetes gene TYK2 regulates β-cell development and its responses to interferon-α

Type 1 diabetes (T1D) is an autoimmune disease that results in the destruction of insulin producing pancreatic {beta}-cells. One of the genes associated with T1D is TYK2, which encodes a Janus kinase with critical roles in type-I interferon (IFN) mediated intracellular signaling. To study the role of TYK2 in human pancreatic {beta}-cell development and response to IFN, we generated TYK2 knockout human iPSCs and directed them into the pancreatic endocrine lineage. Here we show that loss of TYK2 compromised the emergence of endocrine precursors by regulating KRAS expression while mature stem cell-islets (SC-islets) function was not affected. In the maturing SC-islets, the loss or inhibition of TYK2 prevented IFN-induced antigen processing and presentation, including MHC Class I expression in pancreatic endocrine and progenitor cells. Furthermore, in a CD8+ cytotoxic T-cell co-culture model, the survival of {beta}-cells was enhanced by a selective TYK2 inhibitor. These results identify an unsuspected role for TYK2 on {beta}-cell development and support TYK2 inhibition in adult {beta}-cells as a potent therapeutic target to halt T1D progression.

molecular biology↗