Publications by authors named "Markus Kleinewietfeld"

Article Synopsis
  • High salt (HS) intake can worsen immune responses and contribute to the development of hypertensive vascular diseases, particularly after exposure to Ang II, a hormone that raises blood pressure.
  • In experiments with mice, a short period of HS consumption led to increased inflammation and a higher occurrence of severe vascular issues when combined with Ang II infusion, despite no blood pressure differences between groups.
  • The study concludes that transient HS intake triggers a mild immune response that becomes problematic when followed by Ang II exposure, suggesting that HS acts as a precursor to more significant hypertension-related health risks.
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Unlabelled: The pathogenesis of dengue involves a complex interplay between the viral factor and the host immune response. A mismatch between the infecting serotype and the adaptive memory response is hypothesized to lead to exacerbated immune responses resulting in severe dengue. Here, we aim to define in detail the phenotype and function of different regulatory T cell (Treg) subsets and their association with disease severity in a cohort of acute dengue virus (DENV)-infected Cambodian children.

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  • FOXP3+ Tregs in autoimmune conditions lose their suppressive ability and become proinflammatory, complicating Treg therapy for diseases like multiple sclerosis (MS).
  • Research using genetic fate-mapping shows that these dysfunctional Tregs accumulate in the central nervous system and lose their regenerative potential due to interactions with inflamed blood-brain barrier endothelial cells.
  • Treatment with the mTORC1 inhibitor rapamycin can restore Treg function and enhance the effectiveness of autologous Treg therapy for MS patients.
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The use of doxorubicin (DOX) chemotherapy is restricted due to dose-dependent cardiotoxicity. Pyridoxamine (PM) is a vitamin B6 derivative with favorable effects on diverse cardiovascular diseases, suggesting a cardioprotective effect on DOX-induced cardiotoxicity. The cardioprotective nature of PM was investigated in a rat model of DOX-induced cardiotoxicity.

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Mosquito-borne viral infections are on the rise worldwide and can lead to severe symptoms such as haemorrhage, encephalitis, arthritis or microcephaly. A protective immune response following mosquito-borne viral infections requires the generation of a controlled and balanced immune response leading to viral clearance without immunopathology. Here, regulatory T cells play a central role in restoring immune homeostasis.

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In recent years, the gut-central nervous system axis has emerged as a key factor in the pathophysiology of spinal cord injury (SCI). Interleukin-13 (IL-13) has been shown to have anti-inflammatory and neuroprotective effects in SCI. The aim of this study was to investigate the changes in microbiota composition after hemisection injury and to determine whether systemic recombinant (r)IL-13 treatment could alter the gut microbiome, indirectly promoting functional recovery.

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Article Synopsis
  • * High salt consumption can lead to increased heart output, vascular issues, and higher resistance in blood vessels over time.
  • * Recent research suggests that sodium regulates cellular energy and immune functions, prompting a broader definition of salt sensitivity to include these cellular and molecular responses.
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The mammalian holobiont harbors a complex and interdependent mutualistic gut bacterial community. Shifts in the composition of this bacterial consortium are known to be a key element in host health, immunity and disease. Among many others, dietary habits are impactful drivers for a potential disruption of the bacteria-host mutualistic interaction.

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The imbalance between pathogenic and protective T cell subsets is a cardinal feature of autoimmune disorders such as multiple sclerosis (MS). Emerging evidence indicates that endogenous and dietary-induced changes in fatty acid metabolism have a major impact on both T cell fate and autoimmunity. To date, however, the molecular mechanisms that underlie the impact of fatty acid metabolism on T cell physiology and autoimmunity remain poorly understood.

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Article Synopsis
  • FOXP3 regulatory T cells (Tregs) are crucial for preventing autoimmune responses, and their dysfunction can lead to autoimmunity with pro-inflammatory traits.
  • High salt (HS) exposure alters Treg metabolism, mimicking features seen in autoimmune Tregs by disrupting mitochondrial function.
  • The study suggests that short-term high salt intake can lead to long-lasting negative effects on Tregs, potentially increasing the risk of autoimmune conditions, but these effects may be reversible by targeting specific metabolic pathways.
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Colony stimulating factor 2 receptor subunit beta (; CD131) is the common subunit of the type I cytokine receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3 and IL-5. Interestingly, FOXP3 regulatory T cells (Tregs), which play a pivotal role in prevention of autoimmunity have been demonstrated to highly overexpress and genome-wide association studies (GWAS) identified as being linked to autoimmune diseases like multiple sclerosis (MS). However, the exact biological role of CD131 in human Tregs has not been defined yet.

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Failure of remyelination underlies the progressive nature of demyelinating diseases such as multiple sclerosis. Why endogenous repair mechanisms frequently fail in these disorders is poorly understood. However, there is now evidence indicating that this is related to an overly inflammatory microenvironment combined with the intrinsic inability of oligodendrocyte precursor cells (OPCs) to differentiate into mature myelinating cells.

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Research on the microbiome has boomed recently, which resulted in a wide range of tools, packages, and algorithms to analyze microbiome data. Here we investigate and map currently existing tools that can be used to perform visual analysis on the microbiome, and associate the including methods, visual representations and data features to the research objectives currently of interest in microbiome research. The analysis is based on a combination of a literature review and workshops including a group of domain experts.

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The metabolic principles underlying the differences between follicular and marginal zone B cells (FoB and MZB, respectively) are not well understood. Here we show, by studying mice with B cell-specific ablation of the catalytic subunit of glutamate cysteine ligase (Gclc), that glutathione synthesis affects homeostasis and differentiation of MZB to a larger extent than FoB, while glutathione-dependent redox control contributes to the metabolic dependencies of FoB. Specifically, Gclc ablation in FoB induces metabolic features of wild-type MZB such as increased ATP levels, glucose metabolism, mTOR activation, and protein synthesis.

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Dietary habits are amongst the main factors that influence the gut microbiome. Accumulating evidence points to the impact of a high-salt diet (HSD) on the composition and function of the intestinal microbiota, immune system and disease. In the present study, we thus investigated the effects of different NaCl content in the food (0.

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FOXP3 regulatory T cells (Tregs) are central for maintaining peripheral tolerance and immune homeostasis. Because of their immunosuppressive characteristics, Tregs are a potential therapeutic target in various diseases such as autoimmunity, transplantation and infectious diseases like COVID-19. Numerous studies are currently exploring the potential of adoptive Treg therapy in different disease settings and novel genome editing techniques like CRISPR/Cas will likely widen possibilities to strengthen its efficacy.

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Article Synopsis
  • * In vitro studies show that high sodium chloride levels promote the differentiation of T helper 17 cells, which produce IL-17A, a key player in the inflammatory response seen in psoriasis.
  • * Animal models of psoriasis confirmed the findings, demonstrating that increased IL-17A is linked to sodium accumulation in the skin, suggesting potential new treatment strategies targeting this process.
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Autoimmunity is caused by an unbalanced immune system, giving rise to a variety of organ-specific to system disorders. Patients with autoimmune diseases are commonly treated with broad-acting immunomodulatory drugs, with the risk of severe side effects. Regulatory T cells (Tregs) have the inherent capacity to induce peripheral tolerance as well as tissue regeneration and are therefore a prime candidate to use as cell therapy in patients with autoimmune disorders.

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Article Synopsis
  • * The study utilized various advanced technologies to assess how HS influences immune cell activation, highlighting that HS leads to reduced mitochondrial respiration and altered immune responses.
  • * Results showed that while HS improved bactericidal function in certain immune cells (M1-like macrophages), it impaired CD4 T cell migration in others (M2-like macrophages), indicating a complex relationship between salt intake and immune function.
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  • A study of patients with hypertensive metabolic syndrome found that a 5-day fasting period followed by a specific diet led to significant reductions in blood pressure, body mass index, and less need for blood pressure medications compared to diet alone.
  • Fasting was shown to change the gut microbiome, affecting bacteria linked to beneficial short-chain fatty acid production, and certain immune cells like T cells were found to correlate with blood pressure and body weight.
  • Advanced machine learning techniques were used to predict which patients would respond best to fasting based on their immune and microbiome data, suggesting fasting could be an effective non-drug treatment for lowering blood pressure.
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Microglia, the immunocompetent cells of the central nervous system (CNS), play an important role in maintaining cellular homeostasis in the CNS. These cells secrete immunomodulatory factors including nanovesicles and participate in the removal of cellular debris by phagocytosis or autophagy. Accumulating evidence indicates that specifically the cellular exchange of small extracellular vesicles (EVs), participates in physiology and disease through intercellular communication.

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Multiple sclerosis (MS) is a genetically mediated autoimmune disease characterized by inflammation in the central nervous system (CNS). Disease onset is thought to occur when autoreactive T cells orchestrate a cascade of events in the CNS resulting in white and grey matter inflammation and axonal degeneration. It is unclear what triggers the activation of CNS-reactive T cells and their polarization into inflammatory subsets.

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The rise in the prevalence of autoimmune diseases in developed societies has been associated with a change in lifestyle patterns. Among other factors, increased consumption of certain dietary components, such as table salt and fatty acids and excessive caloric intake has been associated with defective immunological tolerance. Dietary nutrients have shown to modulate the immune response by a direct effect on the function of immune cells or, indirectly, by acting on the microbiome of the gastrointestinal tract.

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