Publications by authors named "M Hardtke-Wolenski"

Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of chronic liver disease, especially in patients with severe obesity. However, current mouse models for MASLD do not reflect the polygenetic background nor the metabolic changes in this population. Therefore, we investigated two novel mouse models of MASLD with a polygenetic background for the metabolic syndrome.

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Background: Solid organ transplantation is hindered by immune-mediated chronic graft dysfunction and the side effects of immunosuppressive therapy. Regulatory T cells (Tregs) are crucial for modulating immune responses post-transplantation; however, the transfer of polyspecific Tregs alone is insufficient to induce allotolerance in rodent models.

Methods: To enhance the efficacy of adoptive Treg therapy, we investigated different immune interventions in the recipients.

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Regulatory T cells (Tregs) are a specialized subgroup of T-cell lymphocytes that is crucial for maintaining immune homeostasis and preventing excessive immune responses. Depending on their differentiation route, Tregs can be subdivided into thymically derived Tregs (tTregs) and peripherally induced Tregs (pTregs), which originate from conventional T cells after extrathymic differentiation at peripheral sites. Although the regulatory attributes of tTregs and pTregs partially overlap, their modes of action, protein expression profiles, and functional stability exhibit specific characteristics unique to each subset.

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Background: Alzheimer's disease (AD) is a neurodegenerative disease that remains uncured. Its pathogenesis is characterized by the formation of β-amyloid (Aβ) plaques. The use of antigen-specific regulatory T cells (Tregs) through adoptive transfer has shown promise for the treatment of many inflammatory diseases, although the effectiveness of polyspecific Tregs is limited.

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Article Synopsis
  • Checkpoint inhibitors help restore the function of exhausted CD8 T cells, specifically in the context of chronic infections and cancer, but the exact mechanisms differ across various cancers and are not fully understood.
  • A new HCC (hepatocellular carcinoma) model was created to explore how these inhibitors affect exhausted CD8 tumor-infiltrating lymphocytes, revealing an immune-resistant tumor microenvironment with mostly terminally exhausted T cells.
  • Treatment with PD-1/CTLA-4 blockers increased the presence of progenitor-exhausted CD8 TILs while reducing terminally exhausted cells, suggesting that a few doses of these inhibitors can significantly boost the effectiveness of transferred CD8 T cells in combating tumors.
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