Biology subjects

Renner, L.

Publications and source records attributed to Renner, L..

5 recordsLinked to original sources

bioRxiv2025

Dual Role of Plasmacytoid Dendritic Cells in Humoral and CD8⁺ T Cell Memory Post COVID-19 mRNA Vaccination

The Pfizer-BioNTech coronavirus vaccine (BNT162b2), one of the first nanoparticle-based vaccines approved by the World Health Organisation (WHO), demonstrated 95% efficacy in preventing against Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the precise mechanism of action underlying its effectiveness remains poorly understood. This study investigated the early immune responses in the draining lymph node (dLN) and its role in mediating antiviral protection following vaccination. Here, we focused on the involvement of antigen-presenting cells (APCs) in adaptive immunity. In this study, we demonstrated that the Pfizer-BioNTech coronavirus vaccine is rapidly transported to the dLN and is primarily captured by leukocytes that initiate the expression of the viral antigenic spike protein. Notably, we demonstrated that plasmacytoid dendritic cells (pDCs) are key orchestrators of the inflammatory and humoral response, as their specific depletion led to impaired antibody production and diminished neutralization capacity. Furthermore, single-cell transcriptomic analysis revealed an interaction between pDCs and CD8+ T cells that facilitates T cell activation. In vivo experiments confirmed that pDCs expressing the viral spike protein directly engage with CD8+ T cells, promoting their differentiation and expansion. Moreover, the absence of pDCs affected the formation of antigen-specific memory T cells. Overall, these findings highlight that pDCs are essential players in mediating both adaptive and humoral responses to the Pfizer-BioNTech coronavirus vaccine, providing insights into the mechanistic functioning of mRNA vaccines and establishing a novel role for pDCs as professional APCs.

immunology↗

bioRxiv2025

Tattoo ink induces inflammation in the draining lymph node and impairs the immune response against a COVID-19 vaccine

Despite safety concerns regarding the toxicity of tattoo ink, no studies have reported the consequences of tattooing on the immune response. In this work, we have characterized the transport and accumulation of different tattoo inks in the lymphatic system using a murine model. Upon quick lymphatic drainage, we observed that macrophages mainly capture the ink in the lymph node (LN). An initial inflammatory reaction at local and systemic levels follows ink capture. Notably, the inflammatory process is maintained over time as we observed clear signs of inflammation in the draining LN two months following tattooing. In addition, the capture of ink by macrophages was associated with the induction of apoptosis in both human and murine models. Furthermore, the ink accumulated in the LN altered the immune response against a COVID-19 vaccine. We observed a reduced antibody response following vaccination with a mRNA-based SARS-CoV-2 vaccine, which was associated with a decreased expression of the Spike protein in macrophages in the draining LN. Considering the unstoppable trend of tattooing in the population, our results are crucial in informing the toxicology programs, policymakers, and the general public regarding the potential risk of the tattooing practice associated with an altered immune response.

immunology↗

bioRxiv2024

Tissue-Like Multicellular Development Triggered by Mechanical Compression in Archaea

The advent of clonal multicellularity is a critical evolutionary milestone, seen often in eukaryotes, rarely in bacteria, and only once observed in archaea. We show that uniaxial compression induces clonal multicellularity in haloarchaea, forming tissue-like structures. These archaeal tissues are mechanically and molecularly distinct from their unicellular lifestyle, mimicking several eukaryotic features. Archaeal tissues undergo a multinucleate stage followed by tubulin-independent cellularization, orchestrated by active membrane tension at a critical cell size. After cellularization, tissue junction elasticity become akin to animal tissues and give rise to two cell types--radial peribasal and central apicobasal cells-- with distinct actin and protein glycosylation polarity patterns. Our findings highlight the potential convergent evolution of a biophysical mechanism in the emergence of multicellular systems across domains of life.

cell biology↗

bioRxiv2024

Neural contrast sensitivity is not affected by myopic blur

PurposeThe prevalence of myopia is increasing worldwide, accompanied by an increase of potentially under-corrected myopes. Because the neural pathways processing the retinal image are prone to adaptation in relation to the retinal image quality, we wondered to what extent neural contrast sensitivity (NCS) is altered in the presence of myopic blur. Additionally, the impact of retinal abnormalities like foveal hypoplasia with albinism on NCS was tested. MethodsNCS was psychophysically determined for 11 emmetropic, 23 myopic well-corrected and 15 myopic under-corrected otherwise healthy young (27 {+/-} 6 years) participants and 1 albinism patient. Aberration-free stimulation, independent of the eyes refractive state, was achieved by using a unique spatial light modulator-based interferometric system to bypass the eyes optics. ResultsNo significant differences in NCS were observed between the three groups (Median area-under-curve: 61.9, 62.1, and 62.9 for emmetropes, well-corrected, and under-corrected myopes, respectively; all p > 0.1) but were significantly equivalent between emmetropes and myopes (all p < 0.001). However, the NCS function of the albinism patient differed significantly from the here defined "normal" NCS function. ConclusionsNCS is unaffected by myopic blur and remains stable even for under-correction of up to 1.5 D. This means, that long-term under-corrected myopes still can achieve normal visual acuity as soon as their refractive errors are sufficiently corrected. Furthermore, NCS testing can relate visual deficits to an underlying neurological disorder.

neuroscience↗

bioRxiv2021

Cell Stiffening Contributes to Complement-mediated Injury of Choroidal Endothelial Cells in Early AMD

Age-related macular degeneration (AMD) is the leading cause of blindness in the aging population. Yet, no therapies exist for [~]85% of all AMD patients who have the dry form that is marked by degeneration of the retinal pigment epithelium (RPE) and underlying choroidal vasculature. As the choroidal vessels are crucial for RPE development and maintenance, understanding how they degenerate may lead to effective therapies for dry AMD. One likely causative factor for choroidal vascular loss is the cytolytic membrane attack complex (MAC) of the complement pathway that is abundant on choroidal vessels of humans with early dry AMD. To examine this possibility, we studied the effect of complement activation on choroidal endothelial cells (ECs) isolated from a rhesus monkey model of early AMD that, we report, exhibits MAC deposition and choriocapillaris endothelial loss similar to that seen in human early AMD. Treatment of choroidal ECs from AMD eyes with complement-competent normal human serum caused extensive actin cytoskeletal injury that was significantly less pronounced in choroidal ECs from young normal monkey eyes. We further show that ECs from AMD eyes are significantly stiffer than their younger counterparts and exhibit peripheral actin organization that is distinct from the longitudinal stress fibers in young ECs. Finally, these differences in complement susceptibility and mechanostructural properties were found to be regulated by the differential activity of small GTPases Rac and Rho because Rac inhibition in AMD cells led to simultaneous reduction in stiffness and complement susceptibility while Rho inhibition in young cells exacerbated complement injury. Thus, by identifying cell stiffness and cytoskeletal regulators Rac and Rho as important determinants of complement susceptibility, the current findings offer a new mechanistic insight into choroidal vascular loss in early AMD that warrants further investigation for assessment of translational potential.

pathology↗