Nociceptive Sensory Neurons Drive Interleukin-23 Mediated Psoriasiform Skin Inflammation

The skin has a dual function as a barrier and a sensory interface between the body and the environment. To protect against invading pathogens, the skin harbors specialized immune cells, including dermal dendritic cells (DDCs) and interleukin (IL)-17 producing γδ T cells (γδT17), whose aberrant activation by IL-23 can provoke psoriasis-like inflammation1–4. The skin is also innervated by a meshwork of peripheral nerves consisting of relatively sparse autonomic and abundant sensory fibers. Interactions between the autonomic nervous system and immune cells in lymphoid organs are known to contribute to systemic immunity, but how peripheral nerves regulate cutaneous immune responses remains unclear5,6. Here, we have exposed the skin of mice to imiquimod (IMQ), which induces IL-23 dependent psoriasis-like inflammation7,8. We show that a subset of sensory neurons expressing the ion channels TRPV1 and NaV1.8 is essential to drive this inflammatory response. Imaging of intact skin revealed that a large fraction of DDCs, the principal source of IL-23, is in close contact with these nociceptors. Upon selective pharmacological or genetic ablation of nociceptors9–11, DDCs failed to produce IL-23 in IMQ exposed skin. Consequently, the local production of IL-23 dependent inflammatory cytokines by dermal γδT17 cells and the subsequent recruitment of inflammatory cells to the skin were dramatically reduced. Intradermal injection of IL-23 bypassed the requirement for nociceptor communication with DDCs and restored the inflammatory response12. These findings indicate that TRPV1+NaV1.8+ nociceptors, by interacting with DDCs, regulate the IL-23/IL-17 pathway and control cutaneous immune responses

Diseño de una planta de procesamiento de productos lácteos y elaboración de un plan de contingencia contra deslaves en el Instituto Tecnológico Universitario Guatemala Sur-USAC. Palón, Escuintla.

La presente investigación se realizó en el Instituto Tecnológico Universitario Guatemala Sur, es una dependencia de la Universidad de San Carlos de Guatemala, descentralizada con patrimonio propio, encargado de desarrollar la formación teórica y práctica y la educación profesional en las áreas tecnológicas. Está ubicado en el municipio de Palín, departamento de Escuintla. En el Instituto Tecnológico Universitario Guatemala Sur (ITUGS), se imparten 5 carreras técnicas, dentro de las cuales está la carrera de Técnico en Producción Alimentaria donde se imparte el curso de procesamiento de productos lácteos. La carrera de Técnico necesita el aprendizaje práctico y técnico de la elaboración de alimentos y actualmente el ITUGS no cuenta con las instalaciones adecuadas para desarrollar las prácticas de dicha carrera, por lo que se propone el diseño de una planta de procesamiento de productos lácteos, en donde los alumnos puedan realizar las prácticas de los conocimientos aprendidos en la teoría

Distinct Compartmentalization of the Chemokines CXCL1 and CXCL2 and the Atypical Receptor ACKR1 Determine Discrete Stages of Neutrophil Diapedesis.

Neutrophils require directional cues to navigate through the complex structure of venular walls and into inflamed tissues. Here we applied confocal intravital microscopy to analyze neutrophil emigration in cytokine-stimulated mouse cremaster muscles. We identified differential and non-redundant roles for the chemokines CXCL1 and CXCL2, governed by their distinct cellular sources. CXCL1 was produced mainly by TNF-stimulated endothelial cells (ECs) and pericytes and supported luminal and sub-EC neutrophil crawling. Conversely, neutrophils were the main producers of CXCL2, and this chemokine was critical for correct breaching of endothelial junctions. This pro-migratory activity of CXCL2 depended on the atypical chemokine receptor 1 (ACKR1), which is enriched within endothelial junctions. Transmigrating neutrophils promoted a self-guided migration response through EC junctions, creating a junctional chemokine "depot" in the form of ACKR1-presented CXCL2 that enabled efficient unidirectional luminal-to-abluminal migration. Thus, CXCL1 and CXCL2 act in a sequential manner to guide neutrophils through venular walls as governed by their distinct cellular sources.This work was supported by funds from the British Heart Foundation (FS/14/3/30518 to T.G. and S.N.), the People Programme (Marie Curie Actions) of the EU’s 7th Framework Programme (FP7/2007-2013) under REA grant agreement 608765 (to T.G. and S.N.), and by the Wellcome Trust (098291/Z/12/Z to S.N.). D.S. is supported by the CNIC, SAF2016-79040-R from the Spanish Ministerio de Ciencia, and ERC-2016-CoG 725091 from the European Research Council. M.T. and A.R. are supported by the Sinergia grant CRSII3_160719 of the Swiss National Science Foundation. G.G. is supported by the Wellcome Trust and the MRC. U.H.v.A. and A.T. are supported by the Ragon Institute of MGH, MIT and Harvard and the HMS Center for Immune Imaging

Differential DARC/ACKR1 expression distinguishes venular from non-venular endothelial cells in murine tissues

This work was supported by the National Institutes of Health (NIH) grant AI112521 and the John and Virginia Kaneb Fellowship

Identification et caractérisation, grâce aux lignées de souris dérivées d'individus sauvages, d'une nouvelle population de lymphocytes B conservée dans le genre Mus (les cellules Bw)

L'utilisation de lignées de souris dérivées d individus sauvages nous a permis d identifier une nouvelle sous-population de lymphocytes B, nommée "Bw", qui se distingue par de nombreux critères des sous-populations de cellules B déjà connues chez la souris. Alors que la présence des cellules B-1a CD5pos est quasiment restreinte aux lignées de souris appartenant à la sous-espèce Mus musculus domesticus, les lymphocytes Bw sont conservés à travers l évolution du genre Mus. Les souris de laboratoire ont hérité la population B-1a CD5pos de la sous-espèce M.m. domesticus. Les lymphocytes Bw péritonéaux présentent le phénotype caractéristique suivant : CD19posCD5negMac-1posB220highIgMhighIgDhighCD43negCD9neg. Les cellules Bw sont retrouvées, à des fréquences variables dans la rate, les ganglions, la cavité péritonéale ainsi que les PBL. Le répertoire anticorps de ces lymphocytes est enrichi en spécificités autoréactives contre des antigènes tels que l ADN, la tubuline ou l actine, ainsi qu envers des globules rouges traités par de la broméline. En réponse au LPS et au CpG, ligands des TLR 4 et 9 respectivement, les cellules Bw produisent plus d anticorps anti-PC que les cellules B-2. Il en est de même suite à une immunisation par la bactérie S. pneumoniae. Les précurseurs issus de la moelle osseuse sont capables, au même titre que les précurseurs foetaux, de se différencier en cellules Bw, contrairement aux précurseurs des cellules B-1 qui sont enrichis dans le foie foetal. Ce travail révèle la présence d une nouvelle population de cellules B Mac-1pos, les lymphocytes Bw, conservée à travers l évolution du genre Mus et impliquée dans des réponses immunitaires innées.PARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

IMGT unique numbering for MHC groove G-DOMAIN and MHC superfamily (MhcSF) G-LIKE-DOMAIN

IMGT, the international ImMunoGeneTics information system® (http://imgt.cines.fr) provides a common access to expertly annotated data on the genome, proteome, genetics and structure of immunoglobulins (IG), T cell receptors (TR), major histocompatibility complex (MHC), and related proteins of the immune system (RPI) of human and other vertebrates. The NUMEROTATION concept of IMGT-ONTOLOGY has allowed to define a unique numbering for the variable domains (V-DOMAINs) and constant domains (C-DOMAINs) of the IG and TR, which has been extended to the V-LIKE-DOMAINs and C-LIKE-DOMAINs of the immunoglobulin superfamily (IgSF) proteins other than the IG and TR (Dev Comp Immunol 27:55–77, 2003; 29:185–203, 2005). In this paper, we describe the IMGT unique numbering for the groove domains (G-DOMAINs) of the MHC and for the G-LIKE-DOMAINs of the MHC superfamily (MhcSF) proteins other than MHC. This IMGT unique numbering leads, for the first time, to the standardized description of the mutations, allelic polymorphisms, two-dimensional (2D) representations and three-dimensional (3D) structures of the G-DOMAINs and G-LIKE-DOMAINs in any species, and therefore, is highly valuable for their comparative, structural, functional and evolutionary studie

Wild-derived mouse strains, a valuable model to study B cell responses.

International audienceIn the present report, we revisited the B cell responsiveness of 7 wild-derived mouse strains to various toll-like receptor ligands (TLR-L). We found that 2 of them, namely PWK and STF presented profound defects in B cell proliferative responses to most of the TLR-L. Yet, their macrophage responses were largely unaffected, suggesting that regulation of TLR pathways are distinct in B cells and macrophages. We also showed that, anti-CD40 mAbs rescued the low proliferative responses to CpG in both PWK and STF B cells. In the other hand, CpG synergized with LPS to induce high levels of proliferation in STF B cells, which did not respond to LPS alone. Cytokine or immunoglobulin (Ig) productions, in vitro, were less impaired than the proliferative responses to LPS or CpG alone. In STF B cells, both ERK, P38 and JNK pathways were affected following in vitro TLR4 or TLR9 signaling. Moreover, while the basal levels of Ig secreting cells and of serum Igs were similar to that of control mice, antibody responses to both TI and TD antigens were severely affected, mainly in STF mice. Our findings therefore highlight the relevance of wild-derived mouse strains and TLR-L to study B cell physiology

The Bw cells, a novel B cell population conserved in the whole genus Mus.

International audienceIn common laboratory mouse strains, which are derived from the crossing between three subspecies, peritoneal B cells are enriched in B-1a cells characterized by the CD5(+)Mac-1(+)B220(low)IgM(high)IgD(low)CD43(+)CD9(+) phenotype. Intriguingly in other vertebrates, CD5(+)Mac-1(+) cells have never been found in a specific anatomic site. To ascertain the peculiarity of the CD5(+) peritoneal B cells in laboratory mice, we analyzed the peritoneal B cell subsets in 9 inbred and 39 outbred wild-derived mouse strains belonging to 13 different species/subspecies. We found that most of these strains do not have the CD5(+) B-1a cell population. However, all of these strains including classical laboratory mouse strains, have variable proportions of a novel B cell population: Bw, which is characterized by a unique phenotype (CD5(-)Mac-1(+)B220(high)IgM(high)IgD(high)CD43(-)CD9(-)) and is not restricted to the peritoneal cavity. Bw cells are also distinct from both B-1 and B-2 cells from a functional point of view both by proliferative responses, cytokine secretion and Ab synthesis. Moreover, transfer experiments show that bone marrow and fetal liver cells from wild mice can give rise to Bw cells in alymphoid mice. The conservation of this B cell population, but not of the CD5(+) B-1a, during evolution of the genus Mus, its readiness to respond to TLR ligands and to produce high concentration of autoantibodies suggest that Bw cells play a key role in innate immunity