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Effect of diesel on chemokines and chemokine receptors involved in helper T cell type 1/type 2 recruitment in patients with asthma.

The objective of this study was to evaluate if diesel exhausts could favor helper T cell type (Th) 2-associated allergic reactions either through an increased production of Th2-associated chemokines and of their associated receptors or through a decrease of Th1-attracting chemokines and chemokine receptors. Diesel but not allergen exposure of peripheral blood mononuclear cells from subjects with allergy induced a release of I-309, whereas both diesel and Der p 1 induced an early but transient release of monokine induced by IFN-gamma and a late release of pulmonary and activation-regulated chemokine. Although both Th1- and Th2-attracting chemokines were induced, the resulting effect was an increased chemotactic activity on Th2 but not Th1 cells. Surprisingly, diesel induced a late increase in the expression of the Th1-associated CXC receptor 3 and CC receptor 5. T cell CXC receptor 3 upregulation was not associated with an increased migration to its ligands. These two antagonistic effects have been previously reported as a scavenger mechanism to clear chemokines. Altogether, these results suggest that diesel, even without allergen, may amplify a type 2 immune response but that it can also increase late Th1-associated chemokine receptor expression, perhaps as a scavenger mechanism to clear pro-Th1 chemokines and promote the Th2 pathway.In VitroJournal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Diesel exhaust exposure favors TH2 cell recruitment in nonatopic subjects by differentially regulating chemokine production.

The prevalence of allergic diseases has increased in the last 20 years, and a number of studies have shown that diesel exhaust particle-associated polyaromatic hydrocarbons can exacerbate the allergic reaction. Much less is known about their potential capacity to generate a T(H)2-type allergic reaction in nonatopic subjects.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Chemokine-Induced Cutaneous Inflammatory Cell Infiltration in a Model of Hu-PBMC-SCID Mice Grafted with Human Skin

Recently, certain chemokines and chemokine receptors have been preferentially associated with the selective recruitment in vitro of type 1 T cells, such as IP-10 and its receptor CXCR3, or type 2 T cells such as monocyte-derived chemokine (MDC) and eotaxin and their receptors CCR4 and CCR3. Very few models have provided confirmation of these findings in vivo. Taking advantage of the humanized SCID mouse model grafted with autologous human skin, the ability of the chemokines IP-10, MDC, eotaxin, and RANTES to stimulate cell recruitment was investigated. Intradermal IP-10 injection resulted in an influx of CD4(+) T lymphocytes but also surprisingly in the recruitment of dendritic cells. MDC recruited mainly CD8(+) T lymphocytes, and had little effect on eosinophils. As predicted, eotaxin was a potent inducer of eosinophil and basophil migration, also recruiting CD4(+) T cells. RANTES, a ubiquitous chemokine associated with both type 1 and type 2 profiles, was able to recruit all cell types. CXCR3-positive cells were preferentially recruited by IP-10, whereas CCR3- and CCR4-positive cells were predominantly found after injection of eotaxin and MDC. Thus, in a human environment in vivo, some chemokines have the ability to recruit cells expressing chemokine receptors preferentially expressed on type 1 or type 2 cells. Further investigations revealed that MDC and eotaxin induced the recruitment of type 2, but not type 1, cytokine-producing cells. RANTES, on the other hand, induced the migration of both type 1 and type 2 cytokine-secreting cells, whereas IP-10 did not induce the recruitment of either subtype. These studies provide detailed information on the properties of MDC, eotaxin, IP-10, and RANTES as chemotactic molecules in skin in vivo. The use of the humanized SCID mouse model grafted with human skin is validated as a useful model for the evaluation of chemokine function in the inflammatory reaction, and suggests that therapeutic targeting of certain chemokines might be of interest in diseases associated preferentially with a type 1 or type 2 profile

Involvement of IL-9 in the bronchial phenotype of patients with nasal polyposis.

Nasal polyposis (NP) is frequently associated with asthma. In this disease, asymptomatic bronchial hyperresponsiveness (BHR) is thought to precede the development of asthma. IL-9 and its receptor have been reported as candidate genes for asthma and to be associated with BHR.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Involvement of CCL18 in allergic asthma.

Allergic asthma is associated with a pulmonary recruitment of Th type 2 cells, basophils, and eosinophils, mainly linked to chemokine production. CCL18 is a chemokine preferentially expressed in the lung, secreted by APCs, induced by Th2-type cytokines, and only present in humans. Therefore, CCL18 may be involved in allergic asthma. PBMC from asthmatics allergic to house dust mite cultured in the presence of Dermatophagoides pteronyssinus 1 (Der p 1) allergen secreted CCL18, 48 and 72 h after stimulation, whereas those from healthy donors did not. Part of CCL18 was directly derived from Der p 1-stimulated plasmacytoid dendritic cells, whereas the other part was linked to monocyte activation by IL-4 and IL-13 produced by Der p 1-stimulated T cells. In bronchoalveolar lavages from untreated asthmatic allergic patients, CCL18 was highly increased compared with controls. Functionally, CCL18 preferentially attracted in vitro-polarized Th2 cells and basophils, but not eosinophils and Th1 cells, and induced basophil histamine and intracellular calcium release. These data show a new function for CCL18, i.e. the recruitment of Th2 cells and basophils, and suggest that CCL18 may play a predominant role in allergic asthma.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Pectin remodeling belongs to a homeostatic system and triggers transcriptomic and hormonal modulations

Here, we focused on the biological modifications arisen from a strong and transient variation of the pectin methylesterification status during the seed-to-seedling transition. A reverse genetic approach was used to trigger specific reduction of pectin de-methylesterification during the seed maturation stage and the related physiological effects were assessed using a combination of biochemical, transcriptomic and microscopic analyses. Arabidopsis PME36 is required to implement the characteristic pattern of de-methylesterified pectin in the mature seed. While this pattern is strongly impaired in pme36-1 and pme36-2 mature seed, no phenotypical effect is observed in the knockout mutant during seed germination. By analyzing hormone homeostasis and gene expression regulation, we show a strong and dynamic physiological disorder in the mutant, which reveals the existence of a complex compensatory mechanism overcoming the defect in pectin de-methylesterification. Our results reveal that pectin methylesterification status acts as upstream modulator involved in an undescribed homeostatic system in which pectin remodeling, hormone signaling and transcriptomic regulations interact to ensure the maintenance of a normal seed-to-seedling developmental program

L’enseignement de l’oral à l’école

La plupart des tâches d’apprentissage requièrent un effort conscient et un temps considérables pour passer d’un traitement d’abord contrôlé à un traitement automatique. Ces tâches portent sur des connaissances secondaires et pour lesquelles notre cerveau n’aurait pas eu le temps d’évoluer pour permettre la mise en œuvre d’un processus d’adaptation-imprégnation. A contrario les apprentissages adaptatifs qui ne nécessitent aucun enseignement concernent des connaissances primaires, présentes depuis des milliers d’années, comme le langage oral ou l’évaluation de petites quantités. Une limite très importante des apprentissages adaptatifs relève du fait qu’ils ne permettent pas à l’enfant d’apprendre les connaissances qui font partie de son environnement quotidien. Au moment où un changement d’orientation politique, en France, la refondation de l’école, amène à reconstruire les cycles et à mettre l’accent sur la maîtrise du langage en vue de mieux lutter contre l’échec scolaire, il est utile de faire un point sur cette question  : le langage oral a-t-il besoin d’être enseigné à l’école et si oui, sous quelle forme  ? Le dossier abordera cette question en décrivant la nature réelle du rapport entre l’oral et l’écrit afin de se poser ensuite la question de la nature de l’objet oral à l’école  : objet simplement «  travaillé  » (situations orales plus ou moins contrôlées) ou objet «  enseigné  » (dispositifs et contrats didactiques explicites)  ? L’écrit et l’oral sont-ils si distincts et certaines formes d’oral participent-elles du domaine des «  connaissances secondes  »