BACKGROUND & 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 costimulatory 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.CONCLUSIONS:The subepithelial dome of Peyer's patches contains a unique population of intestinal DC that secretes high levels of lysozyme and internalizes bacteria and dead cells.

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, actinand 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 abT 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 Ca influx and phosphorylation and degradation of the inhibitor of NF-kB (IkB). 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 abT cells in coronin-1A deficient mice, with the exclusion of other lympho/hematopoietic lineages. Citation: Mugnier B, Nal B, Verthuy C, Boyer C, Lam D, et al. (2008) Coronin-1A Links Cytoskeleton Dynamics to TCRab-Induced Cell Signaling. PLoS ONE 3(10): e3467. doi:10.1371/journal.pone.0003467 Editor: Jean Kanellopoulos, University Paris Sud, France Received July 17, 2008; Accepted September 20, 2008; Published October 21, 2008 Copyright: 2008 Mugnier et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by Inserm, CNRS, the ‘Association pour la Recherche sur le Cancer’ (ARC), the ‘Fondation Princesse Grace de Monaco’, and the Commission of the European Communities (to PF); and from the ‘Ministère de l’Education Nationale et de la Recherche’ (ACI #108) (to PF and AA). BN was supported by fellowships from the ‘Ligue Nationale Contre le Cancer’ and ARC. BM was supported by a fellowship from ARC. Competing Interests: The authors have declared that no competing interests exist. * E-mail: ferrier@ciml.univ-mrs.fr . These authors contributed equally to this work.

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 alpha beta T 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-kappaB (I kappa B). 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 alpha beta T cells in coronin-1A deficient mice, with the exclusion of other lympho/hematopoietic lineages.