Homeostatic control of T cells involves tight regulation of effector T cells to prevent excessive activation that can cause tissue damage and autoimmunity. Little is known, however, about whether antigen-presenting cells (APCs) are also involved in maintaining immune system homeostasis once effector T cells are stimulated. Here we found that immature APCs downregulated effector T cell function by a mechanism involving the C-type lectin MGL expressed by APCs. Glycosylation-dependent interactions of MGL with CD45 on effector T cells negatively regulated T cell receptor-mediated signaling and T cell-dependent cytokine responses, which in turn decreased T cell proliferation and increased T cell death. Thus, regulation of effector T cells by MGL expressed on APCs may provide a target for regulating chronic inflammatory and autoimmune diseases.
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http://dx.doi.org/10.1038/ni1390 | DOI Listing |
PLoS One
January 2025
Medical Faculty, Department of Neurology, Otto von Guericke University, Magdeburg, Germany.
For the last 38 years, all neuroprotective agents for patients with ischemic stroke have failed in clinical trials. The innate immune system, particularly microglia, is a much-discussed target for neuroprotective agents. Promising results for neuroprotection by inhibition of integrins with drugs such as natalizumab in animal stroke models have not been translated into clinical practice.
View Article and Find Full Text PDFCancer Immunol Res
January 2025
University of Padua, Padua, PD, Italy.
T cell-based therapies, including Tumor Infiltrating Lymphocyte Therapy (TIL), T cell receptor engineered T cells (TCR T), and Chimeric Antigen Receptor T cells (CAR T), are powerful therapeutic approaches for cancer treatment. While these therapies are primarily known for their direct cytotoxic effects on cancer cells, accumulating evidence indicates that they also influence the tumor microenvironment (TME), by altering the cytokine milieu and recruiting additional effector populations to help orchestrate the antitumor immune response. Conversely, the TME itself can modulate the behaviour of these therapies within the host by either supporting or inhibiting their activity.
View Article and Find Full Text PDFFEBS J
January 2025
Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Canada.
In this study, we explored the intricate relationship between Pannexin 1 (PANX1) and the Hippo signaling pathway effector, Yes-associated protein (YAP). Analysis of The Cancer Genome Atlas (TCGA) data revealed a significant positive correlation between PANX1 mRNA and core Hippo components, Yes-associated protein 1 [YAP], Transcriptional coactivator with PDZ-binding motif [TAZ], and Hippo scaffold, Ras GTPase-activating-like protein IQGAP1 [IQGAP1], in invasive cutaneous melanoma and breast carcinoma. Furthermore, we demonstrated that PANX1 expression is upregulated in invasive melanoma cell lines and is associated with increased YAP protein levels.
View Article and Find Full Text PDFJ Proteome Res
January 2025
Department of Plant Biotechnology and Bioinformatics, Ghent University, 9052 Ghent, Belgium.
Proteomics has become a powerful approach for the identification and characterization of type III effectors (T3Es). Members of the species complex (RSSC) deploy T3Es to manipulate host cells and to promote root infection of, among others, a wide range of solanaceous plants such as tomato, potato, and tobacco. Here, we used TurboID-mediated proximity labeling (PL) in tomato hairy root cultures to explore the proxeomes of the core RSSC T3Es RipU, RipD, and RipB.
View Article and Find Full Text PDFJ Cell Biol
March 2025
Department of Pulmonary Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Epithelial cells can become polyploid upon tissue injury, but mechanosensitive cues that trigger this state are poorly understood. Using an Madin Darby Canine Kidney (MDCK) cell knock-out/reconstitution system, we show that α-catenin mutants that alter force-sensitive binding to F-actin or middle (M)-domain promote cytokinesis failure and binucleation, particularly near epithelial wound-fronts. We identified Leucine Zipper Tumor Suppressor 2 (LZTS2), a factor previously implicated in abscission, as a conformation sensitive proximity partner of α-catenin.
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