Publications by authors named "Wiebke Hansen"

Background: The discrepancy between experimental research and clinical trial outcomes is a persistent challenge in preclinical studies, particularly in stroke research. A possible factor contributing to this issue is the lack of standardization across experimental stroke models, leading to poor reproducibility in multicenter studies. This study addresses this gap by aiming to enhance reproducibility and the efficacy of multicenter studies through the harmonization of protocols and training of involved personnel.

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Opioid addiction presents a relevant health challenge, with chronic heroin use linked to detrimental effects on various aspects of physical, mental, and sociological health. Opioid maintenance therapy (OMT), particularly using methadone, is the primary treatment option for heroin addiction. Previous studies using blood samples from current heroin addicts and OMT patients have shown immunomodulatory effects of heroin and methadone on T cell function.

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Activation of the kallikrein-kinin system promotes vascular leakage, inflammation, and neurodegeneration in ischemic stroke. Inhibition of plasma kallikrein (PK) - a key component of the KKS - in the acute phase of ischemic stroke has been reported to reduce thrombosis, inflammation, and damage to the blood-brain barrier. However, the role of PK during the recovery phase after cerebral ischemia is unknown.

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Peripherally-induced regulatory T cells (pTregs) expressing the retinoic acid receptor-related orphan-receptor gamma t (RORγt) are indispensable for intestinal immune homeostasis. Nuclear factor kappa family members regulate the differentiation of thymic Tregs and promote their survival in the periphery. However, the Treg intrinsic molecular mechanisms controlling the size of the pTregs in the intestine and associated lymphoid organs remain unclear.

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  • Influenza A virus (IAV) causes severe respiratory infections and has implications for both public health and cancer progression, highlighting the need to study interactions between immune responses to cancer and infection.
  • Research using mouse models revealed that IAV infection can decrease tumor burden while activating tumor-specific CD8+ T-cells, linking viral infection with anti-tumor effects.
  • Blocking the migration of these activated CD8+ T-cells from tumors to infected lungs negated the anti-tumoral benefits of IAV infection, emphasizing the complexity of immune interactions in these contexts.
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  • * Infected mice showed increased levels of Nrp-1+CD8+ T cells, which were linked to neurological issues in ECM and liver damage during LCMV infection, indicating a strong activation state of these T cells.
  • * Removing Nrp-1 from T cells led to fewer activated T cells in various organs and reduced disease severity, highlighting Nrp-1's role in worsening T cell responses during
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Retroviral envelope (Env) proteins have long been recognized to exhibit immunosuppressive properties, which affect the CD8 T-cell response to an infection but also to immunization. Interestingly, we previously showed in the Friend murine leukemia virus (F-MuLV) model that the surface Env protein gp70 also plays a role in immunosuppression, in addition to the immunosuppressive function attributed to the transmembrane Env protein. We now demonstrate that immunization with F-MuLV Env leads to a significant increase in interleukin-10 (IL-10)-producing CD4 T cells and that the induction of CD8 T-cell responses in the presence of Env is rescued if the capacity of CD4 T cells to produce IL-10 is abrogated, indicating a mechanistic role of IL-10-producing CD4 T cells in mediating the Env-induced suppression of CD8 T-cell responses in Env co-immunization.

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Background: Friend virus (FV) is a complex of the Friend murine leukemia virus (F-MuLV) and the replication-defective, pathogenic spleen focus forming virus (SFFV). In the past, we used a fluorescently labeled F-MuLV to analyze FV target cells. To build on these findings, we have now created a double-labeled FV that contains a Katushka-labeled F-MuLV and an mTagBFP-labeled SFFV, which we have used to study the infection by the two individual viruses in the FV infection of highly susceptible BALB/c mice.

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Acid sphingomyelinase (Asm) and acid ceramidase (Ac) are parts of the sphingolipid metabolism. Asm hydrolyzes sphingomyelin to ceramide, which is further metabolized to sphingosine by Ac. Ceramide generates ceramide-enriched platforms that are involved in receptor clustering within cellular membranes.

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Acid ceramidase (Ac) is part of the sphingolipid metabolism and responsible for the degradation of ceramide. As bioactive molecule, ceramide is involved in the regulation of many cellular processes. However, the impact of cell-intrinsic Ac activity and ceramide on the course of infection remains elusive.

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Tumor-draining lymph nodes (LNs) play a crucial role during cancer spread and in initiation of anti-cancer adaptive immunity. Neutrophils form a substantial population of cells in LNs with poorly understood functions. Here, we demonstrate that, during head and neck cancer (HNC) progression, tumor-associated neutrophils transmigrate to LNs and shape anti-tumor responses in a stage-dependent manner.

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Background And Purpose: Neonatal encephalopathy caused by hypoxia-ischemia (HI) is a major cause of death and disability in newborns. Clinical and experimental studies suggest a sexual dimorphism in HI-induced brain injury and therapy responses. A major hallmark of HI pathophysiology is the infiltration of peripheral immune cells into the injured brain.

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  • - The study focuses on the role of demethylation in FOXP3-TSDR, which is crucial for the stable differentiation and function of regulatory T (Treg) cells.
  • - Researchers engineered plasmids to express a fusion protein that includes a nonfunctional Cas9 and a TET1 catalytic domain to target the FOXP3-TSDR segment in Jurkat T cells.
  • - Results showed that this approach significantly reduced FOXP3-TSDR methylation and increased Foxp3 mRNA levels in Jurkat cells, suggesting the potential for programming Treg cells in patients.
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  • Graves' orbitopathy (GO) is an autoimmune condition linked to Graves' disease, characterized by inflammation and changes in orbital tissue due to autoantibody action.
  • Researchers developed a mouse model to mimic GO by immunizing with human TSHR A-subunit, allowing the study of early disease progression and immune responses.
  • Findings revealed that macrophage infiltration and hyperthyroid-inducing antibodies appear early in the disease, alongside shifts in T cell populations and increased levels of proinflammatory cytokines.
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Neuropilin-1 (Nrp-1) is a well described marker molecule for CD4Foxp3 thymus-derived regulatory T cells (Tregs). In addition, a small population of CD4Foxp3 conventional (conv) T cells expresses Nrp-1 in naive mice, and Nrp-1 expression has been described to be upregulated on activated CD4 T cells. However, the function of Nrp-1 expression on CD4 non-Tregs still remains elusive.

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The hallmarks of inflammatory bowel disease are mucosal damage and ulceration, which are known to be high-risk conditions for the development of colorectal cancer. Recently, interleukin (IL)-33 and its receptor ST2 have emerged as critical modulators in inflammatory disorders. Even though several studies highlight the IL-33/ST2 pathway as a key factor in colitis, a detailed mode of action remains elusive.

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Neonatal and infant immune responses are characterized by a limited capability to generate protective Ab titers and memory B cells as seen in adults. Multiple studies support an immature or even impaired character of umbilical cord blood (UCB) B cells themselves. In this study, we provide a comprehensive molecular and functional comparison of B cell subsets from UCB and adult peripheral blood.

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  • Colorectal cancer is common globally, and while advances in detection and treatment exist, there's a need for new therapies, especially for advanced cases.
  • Tumor-associated regulatory T cells (Tregs) are prevalent in colorectal cancer patients and may suppress effective immune responses, but targeting these Tregs could enhance antitumoral immunity.
  • Research shows that GPR15, a specific receptor on Tregs, plays a critical role in their migration to colorectal tumors, suggesting that targeting GPR15 could improve immune response and help fight the cancer.
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A wide range of microbial pathogens is capable of entering the gastrointestinal tract, causing infectious diarrhea and colitis. A finely tuned balance between different cytokines is necessary to eradicate the microbial threat and to avoid infection complications. The current study identified IL-33 as a critical regulator of the immune response to the enteric pathogen Citrobacter rodentium.

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Heroin dependence may result in suppression of adaptive immune responses. Previously, we demonstrated an increase in relative numbers of inhibitory CD4 regulatory T cells (Tregs) and impaired proliferative activity of CD4 T cells from heroin-addicted patients in contrast to patients in opioid maintenance therapy and healthy controls. However, it remains elusive whether heroin has a direct impact on the CD4 T cell compartment or whether observed effects result from stressful living conditions.

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The incidence of gastrointestinal infections continues to increase, and infectious colitis contributes significantly to morbidity and mortality worldwide. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) has been discovered to be strongly involved in the intestinal homeostasis. However, whether intestinal CEACAM1 expression has an impact on the control of infectious colitis remains elusive.

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The glycoprotein CD83 is known to be expressed by different immune cells including activated CD4Foxp3 regulatory T cells (Tregs) and CD4Foxp3 conventional T cells. However, the physiological function of endogenous CD83 in CD4 T cell subsets is still unclear. In this study, we have generated a new CD83 mouse line on BALB/c background, allowing for specific ablation of CD83 in T cells upon breeding with CD4-cre mice.

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Inflammatory diseases of the gastrointestinal tract are emerging as a global problem with increased evidence and prevalence in numerous countries. A dysregulated sphingolipid metabolism occurs in patients with ulcerative colitis and is discussed to contribute to its pathogenesis. In the present study, we determined the impact of acid sphingomyelinase (Asm), which catalyzes the hydrolysis of sphingomyelin to ceramide, on the course of -driven colitis.

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Graves' disease (GD) and Graves' orbitopathy are associated with stimulating thyrotropin receptor (TSHR) autoantibodies and autoreactive T cells. Recent studies suggested that sphingosine-1-phosphate (S1P) signaling is involved in the pathogenesis of orbitopathy. In this study, we explored the immune modulatory potential of S1P receptor antagonist fingolimod in a murine model for GD.

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The enzyme acid sphingomyelinase (ASM) hydrolyzes sphingomyelin to ceramide and is thereby involved in several cellular processes such as differentiation, proliferation, and apoptosis in different cell types. However, the function of ASM in T cells is still not well characterized. Here, we used T cell-specific ASM overexpressing mice (t-ASM/CD4cre) to clarify the impact of cell-intrinsic ASM activity on T cell function and .

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