Biology subjects

Hansen, G.

Publications and source records attributed to Hansen, G..

5 recordsLinked to original sources

bioRxiv2026

Fragmented gut-airway microbial networks and airway Moraxella clusters in preschool wheeze

Early-life wheezing in children has been associated with microbial alterations along the gut-airway axis, yet studies simultaneously investigating bacterial communities in both compartments remain scarce. The aim of this cross-sectional exploratory pilot study (n=25) was to characterize and compare nasal and stool bacterial communities in preschool children aged 1-4 years with recurrent wheezing and healthy controls using 16S rRNA gene metabarcoding. Across participants, nasal and stool bacteriomes were highly individualized and taxonomically diverse. Overall richness, evenness, and community composition did not differ significantly between healthy children and wheezers in either compartment. However, wheezers displayed markedly higher within-group variability, particularly in nasal communities. Stratification based on microbiome similarity to healthy samples revealed increased Moraxella and reduced commensal genera including Prevotella spp. and Veillonella, along with lower richness and evenness (all p<0.001) in nasal samples with divergent bacterial communities. Stool alterations were more subtle but included trends toward reduced Bacteroides, Faecalibacterium, and Alistipes in wheezers more divergent from healthy controls. Community assembly in both compartments was largely governed by stochastic processes but accompanied by less complex and more fragmented bacterial interaction networks in wheezing children. Cross-compartment correlations were also altered, most prominently involving stool Lactococcus showing stronger and more numerous correlations with nasal taxa in wheezers than in healthy controls. Divergent wheezers exhibited distinct modular network structure and cross-compartment profiles, consistent with a differentiated microbial organization. Together, these findings suggest compartment-specific differences in microbial interaction patterns across the gut-airway axis in early-life wheezing, despite limited differences in overall community diversity. Take home messagePreschool wheezers showed fragmented gut-airway microbial networks and Moraxella-associated airway community stratification despite limited differences in overall diversity.

microbiology↗

bioRxiv2026

The actin motor protein MYO10 facilitates post-entry spread of respiratory syncytial virus

Human respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infections in infants. However, host factors that influence disease severity remain incompletely defined. While clinical risk factors are known, identifying genetic susceptibility has been challenging. In this study, we combined human genetics with functional virology to identify host factors that modulate RSV infection and spread. Starting from a cohort of infants hospitalized with severe RSV disease, we prioritized rare coding variants present in homozygous form and predicted to cause strong functional impairment, and selected candidate genes for mechanistic follow-up. Functional interrogation of 23 candidates by CRISPR/Cas9 knockout screening in human lung epithelial cells identified unconventional myosin-X (MYO10), encoding the actin-based motor protein myosin-X, as a critical host factor for RSV. Genetic disruption or siRNA-mediated depletion of MYO10 significantly reduced RSV infectivity, with the strongest effects at post-entry stages of the viral life cycle. Loss of MYO10 impaired filopodia formation, cell migration, and wound healing, leading to altered cell-cell connectivity and restricted viral dissemination. MYO10 depletion reduced both short-range cell-to-cell transmission and longer-distance extracellular spread, resulting in fewer infected cells and diminished accumulation of progeny virus in culture supernatants. In contrast, RSV entry, early gene expression, and interferon responses were unaffected. Finally, a rare homozygous MYO10 motor-domain variant (rs7737765; H148Y), enriched in severe cases, also reduced RSV replication in cell culture--opposite to expectations for a risk allele--yet underscoring biological relevance and suggesting that MYO10 variation may influence disease in vivo through additional effects on epithelial function. ImportanceRespiratory syncytial virus (RSV) is a major cause of severe respiratory illness in infants, yet it remains unclear why some children develop more serious disease than others. In this study, we combined patient genetic data with laboratory experiments to identify host factors that influence how RSV spreads in the lung. We found that the human protein MYO10, which mediates the formation of small cell protrusions, plays a key role in enabling the virus to spread from cell to cell. When MYO10 was disrupted, viral spread was strongly reduced, even though early steps of infection were unaffected. Interestingly, a rare genetic variant in MYO10 found in patients also altered viral replication, highlighting potential clinical relevance. These findings provide new insight into how host cell architecture contributes to RSV infection and suggest that targeting host pathways involved in viral spread could complement existing antiviral strategies.

microbiology↗

bioRxiv2026

Tumors accumulate expanded GATA3-dependent tissue Tregs

Targeting Tregs is a potential strategy to improve cancer therapies. However, which Tregs accumulate in response to tumoral processes, and how tumors affect their phenotype, is poorly understood. Here we show that tumor Tregs are equivalent to effector tissue Tregs in steady state organs. We used a mouse model of intestinal neoplasia to demonstrate that one early event in carcinogenesis is sufficient to induce local accumulation of Tregs resembling human tumor Tregs. Treg accumulation was driven by TCR-dependent oligoclonal expansion of tissue Tregs with an effector Treg phenotype. Treg expansion was independent of CCR8, IL33R and CD137, which were previously linked to tumor Treg. In contrast, GATA3 was required for effector tissue Tregs and for their expansion in response to neoplasia. Our findings identify GATA3-dependent clonal expansion of effector tissue Tregs as a key event in promoting tumor growth. HighlightsO_LIAn early tumorigenic event alone drives accumulation of effector tissue Tregs C_LIO_LITregs in tumors are phenotypically akin to effector tissue Tregs C_LIO_LIThe accumulation of Tregs is driven by TCR-dependent oligoclonal expansion C_LIO_LIGATA3 controls tumor-promoting effector tissue Tregs C_LI

immunology↗

bioRxiv2026

Profiling of DNA-methylation signatures in human ILCs during homeostasis and allergic disease

The transcriptional programs of human ILCs are increasingly defined, but the DNA-methylation landscapes that stabilize their identity and function remain poorly understood. Here, we generated genome-wide DNA methylomes of human NK cells, ILC1, ILC2, and ILC3 from blood and lymphoid tissues. Subset-specific differentially methylated regions distinguished all populations and mapped to canonical regulators, including TBX21, GATA3, and RORC, as well as genes not previously linked to ILC biology, such as ERN1, DDX47, JAML, BTLA, and NRROS. Because ILC2 showed a particularly distinct methylation landscape and contribute to allergic inflammation, we tested whether selected ILC2-specific regions were functionally relevant. ILC2 marker regions were largely stable across tissues and during cytokine-driven expansion. CRISPR/Cas9-mediated deletion of the HPGDS or NRROS DMR revealed that these elements act as cis-regulatory sites controlling HPGDS/NRROS expression and promoting production of the type 2 cytokines IL-4, IL-5 and IL-13. Finally, methylome profiling of ILC2 from healthy, atopic, and asthmatic children identified disease-associated DMRs linked to PTGS2, QKI, and GIMAP4. These findings define stable epigenetic signatures of human ILC identity and uncover regulatory elements connecting ILC2 methylation to allergic disease.

immunology↗

bioRxiv2024

Integrative deep immune profiling of the elderly reveals systems-level signatures of aging, sex, smoking, and clinical traits

Elderly individuals have higher disease susceptibility and lower vaccine responsiveness, highlighting the need to better comprehend the aging immune system and its clinical associations. Here we conducted a deep immune profiling study of 550 elderly individuals (61-94 years) and 100 young adults (22-38 years). Utilizing high-dimensional spectral flow cytometry to identify 97 immune cell populations and 48-plex cytokine profiling, we detailed intricate age-and sex-related changes in the elderly immune system at an unprecedented depth. Synthesizing information from clinical, laboratory, and immunological data through an integrative multi-block analysis, we reveal overarching systems-level signatures of aging, such as increased concentrations of specific cytokines and frequencies of defined innate and adaptive immune cell subpopulations. Extending this approach, we identified unique immune signatures of smoking, obesity, and several diseases including osteoporosis, heart failure and gout. Our systems biology approach enables to uncover new relationships between clinical characteristics and immunological traits.

immunology↗