Biology subjects

Bos, S.

Publications and source records attributed to Bos, S..

7 recordsLinked to original sources

bioRxiv2026

cGAS-STING drives alveolar epithelial cell dysfunction in cigarette smoke-induced lung injury

Chronic inflammation induced by cigarette smoke (CS) plays a central role in the pathogenesis of chronic obstructive pulmonary disease (COPD), but its impact on lung epithelial progenitor function and regenerative capacity remains incompletely understood. Here, we combined in vivo and in vitro approaches to dissect how CS exposure and subsequent inflammatory insults shape epithelial repair dynamics. A 6-week whole-body CS exposure model in mice induced lung function impairment and altered gene expression profiles in alveolar epithelial cells, prominently activating interferon (IFN)-related pathways and the cGAS-STING axis. Alveolar epithelial cells from CS-exposed mice generated a similar number, but larger organoids with reduced alveolar differentiation compared to air-exposed mice. Notably, these cells obtained from CS-exposed mice displayed resistance to IFN{gamma}-induced suppression of organoid growth, contrasting with the strong inhibitory effect of IFN{gamma} observed in controls. This phenotype was recapitulated in a two-hit in vitro model using cigarette smoke extract (CSE), in which chronic CSE exposure impaired regeneration and differentiation while inducing resistance to IFN{gamma}. Gene expression and proteomic analyses revealed upregulation of Zbp1, Irf7, and other upstream IFN regulators, correlating negatively with alveolar differentiation potential. Inhibition of the cGAS-STING pathway with RU.521 partially rescued organoid formation, increased proliferation, and alveolar differentiation. Together, our data reveal that CS exposure alters the alveolar epithelial landscape, inducing a stress-adapted, IFN{gamma}-resistant state that compromises alveolar regeneration, with cGAS-STING activation as a key driver of early CS-associated alveolar type 2 cell dysfunction. These findings provide new insight into how chronic inflammation reshapes progenitor cell function during early lung injury.

Cell Biology↗

bioRxiv2026

Dengue virus-specific memory B cell subsets differ as a function of infection history

The four dengue virus serotypes (DENV1-4) are a major global health threat. Infection generates protective immunity over multiple exposures with different serotypes. Virus-specific memory B cells (MBCs) can contribute to lasting protection, yet their development over multiple DENV infections remains undefined. We comprehensively evaluated frequencies of nine DENV-specific B cell subsets in 58 samples from dengue cases, comparing groups with primary (1{degrees}) versus secondary (2{degrees}) DENV infection history. Longitudinal sampling from acute infection to 18 months post-symptom onset enabled assessment of DENV-specific MBC temporal dynamics. Critically, we found that DENV-specific B cell frequency differed substantially at the level of phenotypic subsets in 1{degrees} versus 2{degrees} immunity, despite no significant difference in total frequency of DENV-specific B cells. In particular, DENV-specific IgG+, IgM+, atypical, and class-switched IgD-MBCs were durable until 18 months and accumulated with multiple exposures, representing a bona fide memory compartment against DENV. Also, naive-like IgD+/IgM+ DENV-specific B cells were found. Interestingly, the peak of certain DENV-specific MBCs occurred >3-months post-symptom onset in 2{degrees} DENV immunity, suggesting potential for long-term MBC maturation. We demonstrate that DENV-specific MBC subsets differ as a function of infection history, suggesting that 2{degrees} DENV immunity does not simply generate a quantitative boost, but a qualitative reprogramming of the memory pool. Significance StatementThe four dengue virus serotypes (DENV1-4) cause the most prevalent human mosquito-borne viral disease. Dengue is a febrile disease that often results in debilitating body pain and can rapidly progress to severe disease involving shock. People are generally protected after multiple exposures to different serotypes. Memory B cells (MBCs) can contribute to lasting protection against subsequent dengue. To understand how these rare DENV-specific MBCs develop over multiple exposures, we compared samples from cases with primary versus secondary (i.e., multiple) DENV infections. We found that instead of a higher frequency of total DENV-specific MBCs, particular subsets of DENV-specific MBCs were higher and peaked later after multiple exposures. This suggests that a qualitative shift in DENV-specific MBCs may contribute to protective immunity.

immunology↗

bioRxiv2025

Heightened Play following Play Observation in the Absence of 22KHz Calls in Juvenile Rats

Emotional contagion, the process leading to emotional state matching between individuals is considered a cornerstone for the proper functioning of social groups, via its contribution to group coordination and cohesion, the ability to learn from others and engage in prosocial behaviors. However, to date, most studies of emotional contagion investigate the transfer of negative emotional states thereby bypassing the neurobiology of positive affect sharing. In this study, we aimed to leverage on the innately rewarding and salient nature of play behaviour, to investigate the potential contagiousness of positive affective states in juvenile rats. Observers that had been moderately socially deprived for varying durations first witnessed highly-playful (Play) or non-playful (Control) demonstrator rats prior to being reunited and given the opportunity to freely interact. Surprisingly, we observed the emission of negatively-valenced 22 kHz calls in a subset of sessions which was also associated with heightened play behavior of the demonstrators. We found that the reunited observers showed an increase in play behavior following observation in the Play condition compared to the Control condition, but only after short social isolation and in sessions without 22 kHz calls. In addition, an overall higher number of positively-valenced 50 kHz calls were emitted in the Play condition, again in sessions without 22 kHz emissions. Despite the limitations of the experimental procedure, our results highlight the complex nature of positive emotional sharing and provide encouraging first indications of using social play observation to study positive emotional contagion. Highlights- Social deprivation positively modulates play behavior and USV emission in reunited juvenile rats - Heightened play is associated with 22 kHz USVs following social deprivation - Heightened play was observed following play observation in the absence of 22 kHz USVs - Play observation was associated with an overall increased number of 50 kHz calls emissions - Play observation as an encouraging approach to study positive emotional contagion in rat

animal behavior and cognition↗

bioRxiv2025

Longitudinal Metabolomic Profiling of Biogenic Amines in Plasma and CSF, and Their Correlation, Reveals Sex-Specific and Age Changes in TgF344 Alzheimer's Disease Transgenic and Wildtype Rats

BackgroundAlterations in amine metabolism have been implicated Alzheimers disease (AD). Cerebrospinal fluid (CSF) and plasma are key biofluids in AD research. CSF is considered to better reflect brain metabolic alterations than plasma, while plasma can be obtained more easily. However, plasma-CSF relationships are unclear. AimTo investigate longitudinal changes of amines in plasma and CSF, and their correlation across the two, in male and female TgF344 AD transgenic versus wildtype (WT) rats. MethodLC-MS-based targeted metabolomics was used to analyze 60 and 55 amines in plasma and CSF, respectively, of male and female TgF344-AD and WT rats, at 12, 25, 50 and 85 weeks. Statistical analysis was performed using generalized logistic regressions, Pearson correlations, and differential correlations between groups and matrixes. ResultsCompared to WT controls, at 12 weeks, TgF344-AD rats showed an increase of 3-methylhistidine, anserine, cysteine, s-methylcysteine, while at 25 weeks, male TgF344-AD rats showed pronounced increases in CSF levels of alpha-aminobutyric acid, asparagine, glycylglycine, glycylproline, histidine, isoleucine, kynurenine, leucine, methionine, methionine sulfone, norepinephrine, phenylalanine, proline, tyrosine, and valine. At 50 weeks, female TgF344-AD rats exhibited reductions in CSF for DL-3-aminoisobutyric acid, gamma-aminobutyric acid, ornithine, and putrescine. Distinct plasma-CSF correlations were found for 1-methylhistidine, 2-aminoadipic acid, putrescine, kynurenine, N6,N6,N6-trimethyl-lysine, DL-3-aminoisobutyric acid, and taurine, particularly in TgF344-AD rats. ConclusionsBody fluid, age- and sex-dependent amine alterations in CSF and plasma of TgF344-AD rats compared to WT controls provide important insights into AD disease processes and may aid early diagnosis and therapeutic targeting.

systems biology↗

bioRxiv2022

Differentiation of airway cholinergic neurons from human pluripotent stem cells for airway neurobiology studies

Airway cholinergic nerves play a key role in airway physiology and disease. In asthma and other diseases of the respiratory tract, airway cholinergic neurons undergo plasticity and contribute to airway hyperresponsiveness and mucus secretion. We currently lack mechanistic understanding of airway cholinergic neuroplasticity due to the absence of human in vitro models. Here, we developed the first human in vitro model for airway cholinergic neurons using human pluripotent stem cell (hPSC) technology. hPSCs were differentiated towards mature and functional airway cholinergic neurons via a vagal precursor. Airway cholinergic neurons were characterized by ChAT and VAChT expression, and responded to chemical stimulation with changes in Ca2+ mobilization. Co-culture of hPSC-derived airway cholinergic neurons with airway smooth muscle cells enhanced phenotypic and functional characteristics of these neurons. The differentiation protocol we developed for human airway cholinergic neurons from hPSCs allows for studies into airway neurobiology and airway neuroplasticity in disease.

neuroscience↗

bioRxiv2021

A transcriptomics-guided drug target discovery strategy identifies novel receptor ligands for lung regeneration

Currently, there is no pharmacological treatment targeting defective tissue repair in chronic disease. Here we utilized a transcriptomics-guided drug target discovery strategy using gene signatures of smoking-associated chronic obstructive pulmonary disease (COPD) and from mice chronically exposed to cigarette smoke, identifying druggable targets expressed in alveolar epithelial progenitors of which we screened the function in lung organoids. We found several drug targets with regenerative potential of which EP and IP prostanoid receptor ligands had the most significant therapeutic potential in restoring cigarette smoke-induced defects in alveolar epithelial progenitors in vitro and in vivo. Mechanistically, we discovered by using scRNA-sequencing analysis that circadian clock and cell cycle/apoptosis signaling pathways were enriched in alveolar epithelial progenitor cells in COPD patients and in a relevant model of COPD, which was prevented by PGE2 or PGI2 mimetics. Conclusively, specific targeting of EP and IP receptors offers therapeutic potential for injury to repair in COPD.

pharmacology and toxicology↗

bioRxiv2021

Inhalable textile microplastic fibers impair airway epithelial growth

Synthetic textiles shed fibers that accumulate indoors and this results in continuous exposure when indoors. High exposure to microplastic fibers in nylon flock workers has been linked to the development of airway and interstitial lung disease, but the exact health effects of microplastic fibers on the lungs are unknown. Here we determined effects of polyester and nylon textile microplastic fibers on airway and alveolar epithelial cells using human and murine lung organoids. We observed that particularly nylon microfibers had a negative impact on the growth and development of airway organoids. We demonstrated that this effect was mediated by components leaking from nylon. Moreover, our data suggested that microplastic textile fibers may especially harm the developing airways or airways undergoing repair. Our results call for a need to assess exposure and inhalation levels in indoor environments to accurately determine the actual risk of these fibers to human health. TeaserAirborne fibers shed from synthetic textiles, in particular nylon, can inhibit repair of the cells coating the airways

pharmacology and toxicology↗