Biology subjects

Marchetti, T.

Publications and source records attributed to Marchetti, T..

3 recordsLinked to original sources

bioRxiv2024

Cytokine-Induced Cell Exhaustion to Mitigate Hyperinflammation

Haemophagocytic lymphohistiocytosis (HLH), a life-threatening hyperinflammatory disorder often driven by dysfunctional cytotoxic CD8+ T cells, is marked by cytokine storms, which may follow viral infections. In a study of a perforin-deficient mouse model of HLH with a viral trigger, we aimed to determine if CD8+ T cell behaviour could be modulated by targeted interleukin (IL)-2 treatment. We observed a paradoxical benefit that contrasted with IL-2s typical role in boosting T cell activity: targeted IL-2 delivery to CD8+ T cells led to reduced hyperinflammation and disease severity. Our results demonstrated that IL-2 induced exhaustion in overactive CD8+ T cells, thus mitigating hyperinflammation. These findings highlight the context-dependency of cytokine treatment and suggest new therapeutic strategies for HLH and other inflammatory diseases by leveraging cell exhaustion.

immunology↗

bioRxiv2024

Characterizing an electronic-robotic targeting platform for precise and fast brain stimulation with multi-locus transcranial magnetic stimulation

1.BackgroundMulti-locus TMS (mTMS) enables precise electronic control of brain stimulation targeting, eliminating the need for physical coil movement. However, with a small number of coils, the stimulation area is constrained, and manually handling the coil array is cumbersome. Combining electronic mTMS targeting with robotics will enable automated, user-independent, and precise brain stimulation protocols. ObjectiveCharacterizing an open-source electronic-robotic mTMS platform for rapid and accurate brain stimulation targeting. MethodsWe developed an automated robotic mTMS positioning platform. The accuracy of the system was quantified with a TMS characterizer that measures the TMS-induced electric field on a spherical cortex model. We used a 5-coil mTMS device equipped with a set of five coils coupled to a collaborative robot. The induced electric-field distortion generated by robot coupling was evaluated for each coil. We compared the accuracy of robotic-electronic targeting by repositioning the mTMS coil set with the robotic and the conventional manual positioning. ResultsOur collaborative robot-based system offers submillimeter precision and autonomy in positioning mTMS coil sets. The electronic-robotic mTMS platform was approximately 1.8 mm and 1.0{degrees} more accurate than the conventional manual positioning. Integrating robotics and mTMS automates brain stimulation procedures, resulting in minimal reliance on user expertise and subjective analysis. ConclusionOur open-source platform combining rapid mTMS targeting with robotic precision enhances the safety and reproducibility of brain stimulation techniques, enabling more efficient and reliable outcomes than previous techniques.

neuroscience↗

bioRxiv2019

Gene editing preserves visual function in a mouse model of retinal degeneration

Inherited retinal dystrophies are a large and heterogeneous group of degenerative diseases caused by mutations in various genes. Given the favourable anatomical and immunological characteristics of the eye, gene therapy holds great potential for their treatment. We used a tailored CRISPR/Cas9-based gene editing system to prevent retinal photoreceptor death in the Rd10 mouse model of retinitis pigmentosa. We tested the gene editing tool in vitro and then used in vivo subretinal electroporation to deliver it to one of the retinas of mouse pups at different stages of photoreceptor differentiation. Three months after gene editing, the treated eye exhibited a higher visual acuity compared to the untreated eye. Moreover, we observed preservation of light-evoked responses both in explanted retinas and in the visual cortex of treated animals. Our study validates a CRISPR/Cas9-based therapy as a valuable new approach for the treatment of retinitis pigmentosa caused by autosomal recessive loss-of-function point mutations.

neuroscience↗