Biology subjects

Laffranchi, M.

Publications and source records attributed to Laffranchi, M..

4 recordsLinked to original sources

bioRxiv2026

Systemic-to-mucosal trafficking of memory B cells contributes to humoral immunity in the upper respiratory tract

Systemic vaccination induces serum antibodies and circulating memory B cells, protects from severe disease, but does not ensure sterilizing immunity in the upper respiratory tract, where many respiratory pathogens initiate infection. How systemic memory B cells contribute to mucosal immunity remains unclear. Using multiparametric flow cytometry, single-cell RNA and V(D)J sequencing, and functional analyses of paired blood and nasal/oropharyngeal samples, we characterized human B cells across systemic and mucosal compartments. Swab-derived B cells transcriptionally overlap with circulating activated memory B cells while exhibiting distinct features of activation, tissue retention, and spontaneous IgA/IgG secretion. Approximately 6% of mucosal B-cell clones were shared with blood, indicating systemic-mucosal connectivity. Both infection and vaccination expanded two circulating antigen-specific activated memory B cells subsets, whereas antigen-specific B cells accumulated in the upper respiratory tract only following local inflammation. The finding that B-cell recruitment is reactive rather than preemptive may explain the limited efficacy of parenteral vaccines and provides a rationale for developing integrated systemic-mucosal vaccination strategies.

immunology↗

bioRxiv2023

The impact of gravity on functional movements: kinematic insights and features selection

Exploring the impact of gravity on daily upper-limb movements is crucial for comprehending the complexities of upper-limb impairments. The present study delves into the relationship between the gravitational force and the functional aspects of upper-limb mobility. Starting from 9 pick-and-place tasks, hand trajectories of 24 healthy subjects were acquired using a motion capture system. Five in-use and two novel kinematic metrics were calculated by such trends and tested across conditions. Results suggest movements performed against and propelled by gravity lead to statistically significant changes in motor behaviour in terms of planning, smoothness, efficiency, and accuracy of the movement, underlining the need of differentiating the study of such movements in impaired subjects.

neuroscience↗

bioRxiv2021

SARS-CoV-2-associated ssRNAs activate inflammation and immunity via TLR7/8

The inflammatory and IFN pathways of innate immunity play a key role in both resistance and pathogenesis of Coronavirus Disease 2019 (COVID-19). Innate sensors and SARS-CoV-2-Associated Molecular Patterns (SAMPs) remain to be completely defined. Here we identify single-stranded RNA (ssRNA) fragments from SARS-CoV-2 genome as direct activators of endosomal TLR7/8 and MyD88 pathway. The same sequences induced human DC activation in terms of phenotype and functions, such as IFN and cytokine production and Th1 polarization. A bioinformatic scan of the viral genome identified several hundreds of fragments potentially activating TLR7/8, suggesting that products of virus endosomal processing potently activate the IFN and inflammatory responses downstream these receptors. In vivo, SAMPs induced MyD88-dependent lung inflammation characterized by accumulation of proinflammatory and cytotoxic mediators and immune cell infiltration, as well as splenic DC phenotypical maturation. These results identify TLR7/8 as crucial cellular sensors of ssRNAs encoded by SARS-CoV-2 involved in host resistance and disease pathogenesis of COVID-19.

immunology↗

bioRxiv2018

Characterisation of a type II functionally-deficient variant of alpha-1-antitrypsin discovered in the general population

Lung disease in alpha-1-antitrypsin deficiency (AATD) results from dysregulated proteolytic activity, mainly by neutrophil elastase (HNE), in the lung parenchyma. This is the result of a substantial reduction of circulating alpha-1-antitrypsin (AAT) and the presence in the plasma of inactive polymers of AAT. Moreover, some AAT mutants have reduced intrinsic activity toward HNE, as demonstrated for the common Z mutant, as well as for other rarer variants. Here we report the identification and characterisation of the novel AAT reactive centre loop variant Gly349Arg (p.G373R) present in the ExAC database. This AAT variant is secreted at normal levels in cellular models of AATD but shows a severe reduction in anti-HNE activity. Biochemical and molecular dynamics studies suggest it exhibits unfavourable RCL presentation to cognate proteases and compromised insertion of the RCL into {beta}-sheet A. Identification of a fully dysfunctional AAT mutant that does not show a secretory defect underlines the importance of accurate genotyping of patients with pulmonary AATD manifestations regardless of the presence of normal levels of AAT in the circulation. This subtype of disease is reminiscent of dysfunctional phenotypes in antithrombin and C1-inibitor deficiencies so, accordingly, we classify this variant as the first pure functionally-deficient (type II) AATD mutant.

biochemistry↗