Immune regulation by allergen immunotherapy:lessons learned from experimental approaches

Veel allergische aandoeningen kunnen onderdrukt worden. Er zijn echter nauwelijks medicijnen die de oorzaak van de ziekte aanpakken en die langdurig werkzaam zijn. Dat is ook het geval bij allergische astma. Omdat er over de oorzaak van deze ziekte weinig bekend is, zijn er geen goede medicijnen beschikbaar. Hadi Maazi en Soheila Shirinbak gingen op zoek naar de cellulaire mechanismen die aan allergische astma ten grondslag liggen. De inzichten die dit onderzoek opleverde kunnen wellicht helpen bij de ontwikkeling van een medicijn tegen allergische astma. Maazi en Shirinbak ontdekten dat FoxP3-positieve regulatoire T-cellen belangrijk zijn voor onderdrukking van de luchtwegontsteking die bij allergische astma een rol spelen. B-cellen, plasmacytoide dendritische cellen en CD8-positieve T-cellen daarentegen zijn niet vereist voor de onderdrukking van luchtwegontsteking, luchtweghyperreactiviteit en allergeen-specifiek IgE responsen. Eerder hadden Maazi en Shirinbak al ontdekt dat ook het cytokine IL-10 een belangrijke rol speelt bij de behandeling van allergische astma. In dit proefschrift brengen ze de precieze rol van dit cytokine in kaart. Tenslotte laten ze zien dat CTLA4-Ig en TGFβ de efficiëntie van de SIT behandeling sterk vergroten

Lack of PD-L1 Expression by iNKT Cells Improves the Course of Influenza A Infection

There is evidence indicating that invariant Natural Killer T (iNKT) cells play an important role in defense against influenza A virus (IAV). However, the effect of inhibitory receptor, programmed death-1 (PD-1), and its ligands, programmed death ligand (PD-L) 1 and 2 on iNKT cells in protection against IAV remains to be elucidated. Here we investigated the effects of these co-stimulatory molecules on iNKT cells in the response to influenza. We discovered that compare to the wild type, PD-L1 deficient mice show reduced sensitivity to IAV infection as evident by reduced weight loss, decreased pulmonary inflammation and cellular infiltration. In contrast, PD-L2 deficient mice showed augmented weight loss, pulmonary inflammation and cellular infiltration compare to the wild type mice after influenza infection. Adoptive transfer of iNKT cells from wild type, PD-L1 or PD-L2 deficient mice into iNKT cell deficient mice recapitulated these findings. Interestingly, in our transfer system PD-L1−/−-derived iNKT cells produced high levels of interferon-gamma whereas PD-L2−/−-derived iNKT cells produced high amounts of interleukin-4 and 13 suggesting a role for these cytokines in sensitivity to influenza. We identified that PD-L1 negatively regulates the frequency of iNKT cell subsets in the lungs of IAV infected mice. Altogether, these results demonstrate that lack of PD-L1 expression by iNKT cells reduces the sensitivity to IAV and that the presence of PD-L2 is important for dampening the deleterious inflammatory responses after IAV infection. Our findings potentially have clinical implications for developing new therapies for influenza

Inclusion of CD80 in HSV Targets the Recombinant Virus to PD-L1 on DCs and Allows Productive Infection and Robust Immune Responses

CD80 plays a critical role in stimulation of T cells and subsequent control of infection. To investigate the effect of CD80 on HSV-1 infection, we constructed a recombinant HSV-1 virus that expresses two copies of the CD80 gene in place of the latency associated transcript (LAT). This mutant virus (HSV-CD80) expressed high levels of CD80 and had similar virus replication kinetics as control viruses in rabbit skin cells. In contrast to parental virus, this CD80 expressing recombinant virus replicated efficiently in immature dendritic cells (DCs). Additionally, the susceptibility of immature DCs to HSV-CD80 infection was mediated by CD80 binding to PD-L1 on DCs. This interaction also contributed to a significant increase in T cell activation. Taken together, these results suggest that inclusion of CD80 as a vaccine adjuvant may promote increased vaccine efficacy by enhancing the immune response directly and also indirectly by targeting to DC

Development and pilot testing of the 2019 Canadian Abortion Provider Survey

BACKGROUND: Substantial changes in abortion care regulations, available medications and national clinical practice guidelines have occurred since a 2012 national Canadian Abortion Provider Survey (CAPS). We developed and piloted the CAPS 2019 survey instrument to explore changes of the abortion provider workforce, their clinical care as well as experiences with stigma and harassment. METHODS: We undertook development and piloting in three phases: (1) development of the preliminary survey sections and questions based on the 2012 survey instrument, (2) content validation and feasibility of including certain content aspects via a modified Delphi Method with panels of clinical and research experts, and (3) pilot testing of the draft survey for face validity and clarity of language; assessing usability of the web-based Research Electronic Data Capture platform including the feasibility of complex skip pattern functionality. We performed content analysis of phase 2 results and used a general inductive approach to identify necessary survey modifications. RESULTS: In phase 1, we generated a survey draft that reflected the changes in Canadian abortion care regulations and guidelines and included questions for clinicians and administrators providing first and second trimester surgical and medical abortion. In phase 2, we held 6 expert panel meetings of 5-8 participants each representing clinicians, administrators and researchers to provide feedback on the initial survey draft. Due to the complexity of certain identified aspects, such as interdisciplinary collaboration and interprovincial care delivery differences, we revised the survey sections through an iterative process of meetings and revisions until we reached consensus on constructs and questions to include versus exclude for not being feasible. In phase 3, we made minor revisions based on pilot testing of the bilingual, web-based survey among additional experts chosen to be widely representative of the study population. Demonstrating its feasibility, we included complex branching and skip pattern logic so each respondent only viewed applicable questions based on their prior responses. CONCLUSIONS: We developed and piloted the CAPS 2019 survey instrument suitable to explore characteristics of a complex multidisciplinary workforce, their care and experience with stigma on a national level, and that can be adapted to other countries

Emerging roles of innate lymphoid cells in inflammatory diseases: clinical implications

Innate lymphoid cells (ILC) represent a group of lymphocytes that lack specific antigen receptors and are relatively rare as compared to adaptive lymphocytes. ILCs play important roles in allergic and nonallergic inflammatory diseases due to their location at barrier surfaces within the airways, gut, and skin, and they respond to cytokines produced by activated cells in their local environment. Innate lymphoid cells contribute to the immune response by the release of cytokines and other mediators, forming a link between innate and adaptive immunity. In recent years, these cells have been extensively characterized and their role in animal models of disease has been investigated. Data to translate the relevance of ILCs in human pathology, and the potential role of ILCs in diagnosis, as biomarkers and/or as future treatment targets are also emerging. This review, produced by a task force of the Immunology Section of the European Academy of Allergy and Clinical Immunology (EAACI), encompassing clinicians and researchers, highlights the role of ILCs in human allergic and nonallergic diseases in the airways, gastrointestinal tract, and skin, with a focus on new insights into clinical implications, therapeutic options, and future research opportunities

Conversion of Monte Carlo Steps to Real Time for Grain Growth Simulation

Monte Carlo (MC) technique is becoming a very effective simulation method for prediction and analysis of the grain growth kinetics at mesoscopic level. It should be noted that MC models have no real time of physical systems due to the probabilistic nature of this simulation technique. This leads to difficulties when converting simulated time, the Monte Carlo steps tMCS, to real time. The correspondence between Monte Carlo steps and real time should be proposed for comparing the kinetics of MC models with the experiments. In this work, the conversion of Monte Carlo steps to real time is attempted. The lattice sites spacing Δ and the temperature T cannot be ignored in the Monte Carlo simulation of grain growth. Real time will be associated with tMCS, T, and Δ

Conception and realization of microwaves and millimeter waves systems for non destructive testing (apllication to embedded defects profile and image restoration)

Les techniques microondes et millimétriques sont bien adaptées pour le Contrôle Non Destructif (CND) de matériaux mais celles-ci ne sont pas encore. utilisées à grande échelle dans un contexte industriel. L'analyseur de réseaux vectoriel (ARV) jusqu'ici considéré comme un outil de choix dans le domaine de la caractérisation microondes en laboratoire s'avère souvent surdimensionné pour beaucoup d'applications industrielles. Ce travail consiste donc à proposer un dispositif, le "S-Parameters Measurement System" (SPMS), permettant la mesure d'un coefficient de réflexion S11, il est conçu dans une optique de simplicité et de faible coût. Deux démonstrateurs ont été réalisés, les SPMS-35000 et SPMS-60000 fonctionnant respectivement à 35 GHz et 60 GHz. La mesure du S11 en espace libre d'un matériau sous test, a d'abord permis la détection et la localisation de défauts de petite taille (quelques mm) enfouis dans un matériau diélectrique. Puis, l'utilisation d'outils de traitement de signal permettant la résolution du problème inverse, la déconvolution aveugle et les réseaux de neurones artificiels, a rendu possible l'évaluation de la géométrie et de la profondeur du défaut.LILLE1-BU (590092102) / SudocSudocFranceF

Prévalence et facteurs prédictifs du no reflow au cours du syndrome coronarien aigu avec en sus décalage persistant du segment ST

LIMOGES-BU Médecine pharmacie (870852108) / SudocSudocFranceF

Immune regulation by allergen immunotherapy : lessons learned from experimental approaches

Veel allergische aandoeningen kunnen onderdrukt worden. Er zijn echter nauwelijks medicijnen die de oorzaak van de ziekte aanpakken en die langdurig werkzaam zijn. Dat is ook het geval bij allergische astma. Omdat er over de oorzaak van deze ziekte weinig bekend is, zijn er geen goede medicijnen beschikbaar. Hadi Maazi en Soheila Shirinbak gingen op zoek naar de cellulaire mechanismen die aan allergische astma ten grondslag liggen. De inzichten die dit onderzoek opleverde kunnen wellicht helpen bij de ontwikkeling van een medicijn tegen allergische astma. Maazi en Shirinbak ontdekten dat FoxP3-positieve regulatoire T-cellen belangrijk zijn voor onderdrukking van de luchtwegontsteking die bij allergische astma een rol spelen. B-cellen, plasmacytoide dendritische cellen en CD8-positieve T-cellen daarentegen zijn niet vereist voor de onderdrukking van luchtwegontsteking, luchtweghyperreactiviteit en allergeen-specifiek IgE responsen. Eerder hadden Maazi en Shirinbak al ontdekt dat ook het cytokine IL-10 een belangrijke rol speelt bij de behandeling van allergische astma. In dit proefschrift brengen ze de precieze rol van dit cytokine in kaart. Tenslotte laten ze zien dat CTLA4-Ig en TGFβ de efficiëntie van de SIT behandeling sterk vergroten. In this PhD thesis we aimed to unravel the mechanism of action of SIT at cellular level on the one hand and find ways to improve the efficacy of SIT in the other hand in a mouse model of allergic asthma. We found that while FOXP3+ regulatory T cells play a role in SIT-induced suppression of airway eosinophilia, CD8+ T cells, B cells and plasmacytoid dendritic cells play dispensable roles in SIT-induced suppression of airway hyperreactivity, airway eosinophilia and allergen-specific IgE levels in the serum.

Evaluation de protocoles d'hygiène bucco-dentaire dans deux établissements d'hébergement pour personnes âgées de l'agglomération de Nancy

NANCY1-SCD Pharmacie-Odontologie (543952101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF