Biology subjects

Nelissen, S.

Publications and source records attributed to Nelissen, S..

3 recordsLinked to original sources

bioRxiv2025

Epithelial-Mesenchymal Plasticity is Associated with Immunosuppressive Features in Canine Mammary Carcinomas

Epithelial-mesenchymal plasticity (EMP) is a cellular process activated in carcinoma cells to drive invasiveness, metastasis, and chemoresistance. Recently, we have demonstrated that activation of the EMP program also results in the assembly of an immunosuppressive tumor microenvironment and resistance to immunotherapy in an immunocompetent orthotopic murine model. However, it has yet to be shown whether these findings can be translated to canine carcinomas. Here, we show that in spontaneous canine mammary carcinomas (CMCs), which share similar histopathologic, molecular, and clinical features with human breast cancers, EMP activation is linked to the recruitment of immunosuppressive cells including regulatory T-cells and M2-like macrophages. Additionally, through transcriptomic profiling of CMCs, we identify that the glycoprotein CD109 is associated with EMP-mediated immunosuppression across canine, murine, and human breast cancer models. CD109 has been previously associated with tumorigenicity, but not immunosuppression in cancers of any species. Finally, we identified upregulation of several immunosuppressive paracrine factors across multiple canine carcinomas, including oral squamous cell carcinoma, urothelial carcinoma, and pulmonary carcinoma samples. These findings demonstrate for the first time that the EMP program is associated with immunosuppression in canine carcinomas, with direct translational implications for human breast cancers.

cancer biology↗

bioRxiv2025

Diverse microbial exposure exacerbates the development of allergic airway inflammation in adult mice

BackgroundExposure to a diversity of microbes has been implicated in playing a major role in susceptibility to the development of allergic lung type diseases. The hygiene hypothesis suggests that those exposed to a broad diversity of microbes are more likely to be protected against developing allergic type diseases. However, changes in exposure to microbial diversity can occur in both younger individuals, as well as in adults, and the effects are not always understood. ObjectiveWe investigated the effect of exposure to broad microbial diversity on the airway T cell response in house dust mite (HDM) induced allergic airway disease (AAD, a model of allergic asthma). MethodsWe increased exposure to broad microbial diversity by co-housing specific pathogen free (SPF) adult or newborn mice with pet store mice (PSE or BiPSE, respectively). Mice were then exposed to HDM to induce AAD. ResultsWe found that the effect of increased microbial exposure on the development of allergic airway inflammation differs by age. Increasing exposure to diverse microbes as adults exacerbates the development of allergic airway inflammation, whereas this was not observed when exposure occurred at birth. ConclusionWe suggest that experimental evaluation of the hygiene hypothesis in inflammation, particularly those using mouse models, may need to consider age of the host and time of microbial exposure. Capsule SummaryMouse models of increased exposure to diverse microbial environment shown to differentially affect the development of allergic airway inflammation, depending on the age of microbial exposure.

immunology↗

bioRxiv2022

Disrupted development and altered hormone signaling in male Padi2/Padi4 double knockout mice

BackgroundPeptidylarginine deiminase enzymes (PADs) convert arginine residues to citrulline in a process called citrullination or deimination. Recently, two PADs, PAD2 and PAD4, have been linked to hormone signaling in vitro and the goal of this study was to test for links between PAD2/PAD4 and hormone signaling in vivo. MethodsPreliminary analysis of Padi2 and Padi4 single knockout (SKO) mice did not find any overt reproductive defects and we predicted that this was likely due to genetic compensation. To test this hypothesis, we created a Padi2/Padi4 double knockout (DKO) mouse model and tested these mice along with wild-type FVB/NJ (WT) and both strains of SKO mice for a range of reproductive defects. ResultsControlled breeding trials found that male DKO mice appeared to take longer to have their first litter than WT controls. This tendency was maintained when these mice were mated to either DKO and WT females. Additionally, unsexed 2-day old DKO pups and male DKO weanlings both weighed significantly less than their WT counterparts, took significantly longer than WT males to reach puberty, and had consistently lower serum testosterone levels. Furthermore, 90-day old adult DKO males had smaller testes than WT males with increased rates of germ cell apoptosis. ConclusionsThe Padi2/Padi4 DKO mouse model provides a new tool for investigating PAD function and outcomes from our studies provide the first in vivo evidence linking PADs with hormone signaling.

molecular biology↗