Coronin-1A Links Cytoskeleton Dynamics to TCRαβ-Induced Cell Signaling

Actin polymerization plays a critical role in activated T lymphocytes both in regulating T cell receptor (TCR)-induced immunological synapse (IS) formation and signaling. Using gene targeting, we demonstrate that the hematopoietic specific, actin- and Arp2/3 complex-binding protein coronin-1A contributes to both processes. Coronin-1A-deficient mice specifically showed alterations in terminal development and the survival of αβT cells, together with defects in cell activation and cytokine production following TCR triggering. The mutant T cells further displayed excessive accumulation yet reduced dynamics of F-actin and the WASP-Arp2/3 machinery at the IS, correlating with extended cell-cell contact. Cell signaling was also affected with the basal activation of the stress kinases sAPK/JNK1/2; and deficits in TCR-induced Ca2+ influx and phosphorylation and degradation of the inhibitor of NF-κB (IκB). Coronin-1A therefore links cytoskeleton plasticity with the functioning of discrete TCR signaling components. This function may be required to adjust TCR responses to selecting ligands accounting in part for the homeostasis defect that impacts αβT cells in coronin-1A deficient mice, with the exclusion of other lympho/hematopoietic lineages

Prédiction de l'efficacité de l'infliximab dans le traitement de la polyarthrite rhumatoïde (rôle du polymorphisme-308 du gène du Tumor Necrosis Factor alfa)

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Pathogenic bacteria and dead cells are internalized by a unique subset of Peyer's Patch dendritic cells that express lysozyme.

International audienceBACKGROUND & AIMS:: Lysozyme has an important role in preventing bacterial infection. In the gastrointestinal tract, lysozyme is thought to be mainly expressed by Paneth cells of the crypt epithelium. We investigated its expression in the Peyer's patch-a major intestinal site of antigen sampling and pathogen entry. METHODS:: We performed immunostaining on normal and Salmonella Typhimurium-infected intestinal samples and analyzed them by confocal microscopy and flow cytometry. RESULTS:: In Peyer's patch of mouse, rat, and human, lysozyme was strongly expressed in the germinal center of follicles by tingible body macrophages and in the subepithelial dome by a subset of myeloid dendritic cells (DC). Among DC subsets from mouse Peyer's patches, these lysozyme-expressing DC displayed the highest surface expression of class II major histocompatibility complex and co-stimulatory molecules; they were the most efficient at capturing microspheres in vitro. Moreover, they were the main DC subset involved in bacterial pathogen uptake and in dead cell clearance, including M cells. CONCLUSION:: The subepithelial dome of Peyer's patches contains a unique population of intestinal DC that secrete high levels of lysozyme and internalize bacteria and dead cells

Impact of care pathway for nursing home residents treated for cancer: ONCO-EHPAD study

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