Biology subjects

Freund, L.

Publications and source records attributed to Freund, L..

3 recordsLinked to original sources

bioRxiv2025

Immunological liver-skin axis: a systemic Vγ4+ γδT17 cell responselinks psoriasis-like inflammation and MASLD

Metabolic dysfunction-associated steatotic liver disease (MASLD) and psoriasis frequently co-occur and share interleukin-17 (IL-17)-mediated inflammatory mechanisms. Using a murine model combining Western-diet-induced early MASLD with chronic imiquimod-triggered psoriasis-like dermatitis, we observed exacerbated skin inflammation with increased cellularity and systemic IL-17-driven immune activation. In mice with psoriasis-like skin inflammation, hepatic {gamma}{delta}T cells shifted from IFN-{gamma}-producing {gamma}{delta}T1 toward IL-17-secreting {gamma}{delta}T17 cells, accompanied by an acute-phase response and induction of hepatic lipogenic gene expression. Single-cell RNA sequencing revealed an expansion of V{gamma}4 {gamma}{delta}T17 cells engaged in IL-17 and TGF-{beta} signaling, consistent with early fibrogenic responses. Together, these findings identify V{gamma}4 {gamma}{delta}T17 cells as a mechanistic link between psoriasis and MASLD, promoting systemic inflammation and early hepatic remodeling. Consistently, in a clinical cohort of patients with moderate-to-severe psoriasis and co-morbid MASLD, IL-17-targeted therapy improved hepatic steatosis, underscoring the translational relevance of this immunological axis.

immunology↗

bioRxiv2025

Lung microbiomes variable responses to dust exposure

Inhalation of dust is significant and relevant to health effects. As pollution and climate change worsen in dryland regions, wind currents entrain loose sediment and dust. This potentially disperses toxic geochemical and microbial burdens throughout the region. When inhaled environmental dust and host-associated microbiomes mingle, they pose exposure risks to host respiratory health. The Salton Sea, Californias largest lake, is shrinking thus exposing nearby communities to playa dust. Therefore, we analyze the effect of Salton Sea dust exposure in murine models to relate lung microbial communities and respiratory health. We used an environmental chamber to expose mice to dust filtrate or ambient air and examined the effects of those exposures on lung microbiomes. We found that lung microbial composition varied by dust exposure. Furthermore, dust elicited neutrophil recruitment and immune responses more than mice exposed to ambient air. Sources of dust differentially affected the composition of the lung core microbiome. Lung microbial diversity correlated with neutrophil recruitment as lungs associated with inflammatory responses harbored more diverse microbiomes. Although Salton Sea dust influences dust microbiomes and prevalent taxa, these responses were variable. The composition of lungs exposed to dust collected further from the Sea was more similar to lungs from ambient air exposures; in contrast, dust collected near the Sea yielded lung microbiomes that clustered further from lungs exposed to ambient air. As lakes continue to dry out, we expect greater public health risks in proximal dryland regions, which may correlate with dust microbial dispersal-related changes to lung microbiomes. ImportanceDust inhalation can lead to health effects, especially when toxic chemicals and microbes mix in with the dust particles. As Californias Salton Sea dries up, it exposes lake bottom sediments to wind, which disperses the dried sediments. To mimic the effect of inhaling Salton Sea dust, we collected and filtered airborne dust to use in exposure experiments with mice in environmental chambers. We predicted that inhaling small dust particles, chemicals, and microbial residues found in this dust would affect mouse respiratory health, or change the microbes found inside their lungs. We found that inhaling dust led to lung inflammation and the dust source influenced the type of microbes found inside mouse lungs. As lakes continue to dry out, we expect greater health risks and changes to lung microbiomes. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=95 SRC="FIGDIR/small/648223v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@11e791eorg.highwire.dtl.DTLVardef@1a1a853org.highwire.dtl.DTLVardef@31ee4aorg.highwire.dtl.DTLVardef@135f40_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2020

Hidden paths to endless forms most wonderful: Parasite-blind diversification of host quality

Evolutionary diversification can occur in allopatry or sympatry, can be unselected or driven by selection, and can be phenotypically manifested immediately or remain phenotypically latent until later manifestation in a newly encountered environment. Diversification of host-parasite interactions is frequently studied in the context of intrinsically selective coevolution, but the potential for host-parasite interaction phenotypes to diversify latently during parasite-blind evolution is rarely considered. Here we use a social bacterium experimentally adapted to several environments in the absence of phage to analyse allopatric diversification of latent host quality - the degree to which a host population supports a viral epidemic. Phage-blind evolution reduced host quality overall, with some bacteria becoming completely resistant to growth suppression by phage. Selective-environment differences generated only mild divergence in host-quality. However, selective environments nonetheless played a major role in shaping evolution by determining the degree of stochastic diversification among replicate populations within treatments. Ancestral motility genotype was also found to strongly shape patterns of latent hostquality evolution and diversification. These outcomes show that adaptive landscapes can differ in how they constrain stochastic diversification of a latent phenotype and that major effects of selection on biological diversification can be missed by focusing on trait means. Collectively, our findings suggest that latent-phenotype evolution (LPE) should inform host-parasite evolution theory and that diversification should be conceived broadly to include latent phenotypes.

evolutionary biology↗