Mouse Natural Killer (NK) Cells Express the Nerve Growth Factor Receptor TrkA, which Is Dynamically Regulated

Background: Nerve growth factor (NGF) is a neurotrophin crucial for the development and survival of neurons. It also acts on cells of the immune system which express the NGF receptors TrkA and p75 NTR and can be produced by them. However, mouse NK cells have not yet been studied in this context. Methodology/Principal Findings: We used cell culture, flow cytometry, confocal microscopy and ELISA assays to investigate the expression of NGF receptors by NK cells and their secretion of NGF. We show that resting NK cells express TrkA and that the expression is different on NK cell subpopulations defined by the relative presence of CD27 and CD11b. Expression of TrkA is dramatically increased in IL-2-activated NK cells. The p75 NTR is expressed only on a very low percentage of NK cells. Functionally, NGF moderately inhibits NK cell degranulation, but does not influence proliferation or cytokine production. NK cells do not produce NGF. Conclusions/Significance: We demonstrate for the first time that mouse NK cells express the NGF receptor TrkA and tha

PI3Kγ is a molecular switch that controls immune suppression

Macrophages play critical, but opposite, roles in acute and chronic inflammation and cancer1,2,3,4,5. In response to pathogens or injury, inflammatory macrophages express cytokines that stimulate cytotoxic T cells, whereas macrophages in neoplastic and parasitic diseases express anti-inflammatory cytokines that induce immune suppression and may promote resistance to T cell checkpoint inhibitors1,2,3,4,5,6,7. Here we show that macrophage PI 3-kinase γ controls a critical switch between immune stimulation and suppression during inflammation and cancer. PI3Kγ signalling through Akt and mTor inhibits NFκB activation while stimulating C/EBPβ activation, thereby inducing a transcriptional program that promotes immune suppression during inflammation and tumour growth. By contrast, selective inactivation of macrophage PI3Kγ stimulates and prolongs NFκB activation and inhibits C/EBPβ activation, thus promoting an immunostimulatory transcriptional program that restores CD8+ T cell activation and cytotoxicity. PI3Kγ synergizes with checkpoint inhibitor therapy to promote tumour regression and increased survival in mouse models of cancer. In addition, PI3Kγ-directed, anti-inflammatory gene expression can predict survival probability in cancer patients. Our work thus demonstrates that therapeutic targeting of intracellular signalling pathways that regulate the switch between macrophage polarization states can control immune suppression in cancer and other disorders

The Four types of Tregs in malignant lymphomas

Regulatory T cells (Tregs) are a specialized subpopulation of CD4+ T cells, which act to suppress the activation of other immune cells. Tregs represent important modulators for the interaction between lymphomas and host microenvironment. Lymphomas are a group of serious and frequently fatal malignant diseases of lymphocytes. Recent studies revealed that some lymphoma T cells might adopt a Treg profile. Assessment of Treg phenotypes and genotypes in patients may offer prediction of outcome in many types of lymphomas including diffuse large B-cell lymphoma, follicular lymphoma, cutaneous T cell lymphoma, and Hodgkin's lymphoma. Based on characterized roles of Tregs in lymphomas, we can categorize the various roles into four groups: (a) suppressor Tregs; (b) malignant Tregs; (c) direct tumor-killing Tregs; and (d) incompetent Tregs. The classification into four groups is significant in predicting prognosis and designing Tregs-based immunotherapies for treating lymphomas. In patients with lymphomas where Tregs serve either as suppressor Tregs or malignant Tregs, anti-tumor cytotoxicity is suppressed thus decreased numbers of Tregs are associated with a good prognosis. In contrast, in patients with lymphomas where Tregs serve as tumor-killing Tregs and incompetent Tregs, anti-tumor cytotoxicity is enhanced or anti-autoimmune Tregs activities are weakened thus increased numbers of Tregs are associated with a good prognosis and reduced numbers of Tregs are associated with a poor prognosis. However, the mechanisms underlying the various roles of Tregs in patients with lymphomas remain unknown. Therefore, further research is needed in this regard as well as the utility of Tregs as prognostic factors and therapy strategies in different lymphomas

Prise en charge des familles migrantes en PMI sur un territoire urbain de la Somme

Dans leur pratique, les professionnels de santé se retrouvent confrontés à des patients migrants. La population migrante, qui s est diversifiée au cours du temps en France, représente une population souvent vulnérable, tant physiquement que psychologiquement. Améliorer l état de santé des migrants est devenu un objectif de santé publique. A travers l expérience de professionnels de PMI (Protection Maternelle et infantile) exerçant sur un territoire urbain de la Somme, se dégagent les spécificités de la prise en charge des familles migrantes lors des consultations de nourrissons. La barrière de la langue est un premier obstacle et obtenir l assistance d un interprète professionnel n est pas toujours évident. La culture de l Autre doit être prise en compte pour adapter la conduite préventive et thérapeutique, sans oublier que la situation socio-économique et administrative souvent complexe des migrants interfère dans les soins et le bien-être de l enfant. La présente enquête montre que par conséquent, les formations sur les migrants et les facteurs qui interviennent dans leur accès aux soins sont nécessaires dans le cursus initial et dans la formation continue selon les besoins. Le praticien, doit être à l écoute du patient, s informer et s interroger sur ses propres représentations, afin de constamment adapter sa pratique pour une démarche respectueuse et efficace..In their practice, the healthcare professionals take care of immigrant patients. The migrant population, which become more and more diverse in France, often represents a vulnerable group, physically and psychologically. Improving the health of migrants became a matter of public health. Based on the experience of professionals working in Maternal-child health centers in an urban area of the Somme, we could identify some specificities in the care of the immigrant families. Language is the first barrier and to obtain the assistance of a professional interpreter is not easy. The culture of the patients must be taken into account to adapt the preventive and therapeutic conduct. But the complex economic and social status of the migrants must not be forgotten, as it interferes in the care and the well-being of the child. The present survey shows that the healthcare professionals must learn about the migrants and the factors of their health status, during their early studies and afterwards. The practitioner has to listen to the patient, inquire and wonder about his own representations, to adapt constantly his practice for a respectful and effective approach.AMIENS-BU Santé (800212102) / SudocSudocFranceF

Contributions of Intermolecular Interactions between Constitutive Arabinoxylans to the Flaxseeds Mucilage Properties

International audienceThe main fraction (about 75%) of the mucilage extracted from seeds of Linum usitatissimum which consists of arabino-xylans (AX) has been studied in dilute and semidilute regimes by SEC/MALLS analysis and rheology, respectively. It has been found that AX contains 3 populations of about 5 000 000 g mol-1 (less than 10%), 1 000 000 g mol-1 (about 40%), and 200 000 g mol-1 (about 50%). We have also observed a great retention of polymer during the filtration procedure, which is much pronounced as the AX concentration increases. This evidences the presence of large aggregates in the solution. The retention can be greatly diminished if the filtration is conducted under higher temperature. Aggregation could result from the establishment of intermolecular associations via hydrogen bonds. This hypothesis seems to be confirmed by the two higher populations in molar masses which present a random coil conformation consistent with a low degree of branching. Rheological measurements, conducted at 20 g L-1, have confirmed the association tendency leading to pseudo gels behavior. Viscoelastic properties have been evidenced by time−temperature master curves of dynamic spectra. Such master curves have also been established with addition of chaotropic (i.e., KSCN) and lyotropic (i.e., NaCl) salts. It has been shown that intermolecular associations are greatly diminished under chaotropic salts influence. This has been also confirmed by SEC/MALLS analysis. These results point out the role of hydrogen bonds in the organization of the AX system

Flax ( Linum usitatissimum ) Seed Cake: A Potential Source of High Molecular Weight Arabinoxylans?

International audienceWater-soluble polysaccharides were extracted from flaxseed cake and analyzed. Two groups were separated by anion-exchange chromatography. The first one (nonretained) was the major fraction (83%) and possessed a high molecular weight (HMW) arabinoxylan (56%) with an Ara/Xyl ratio of 0.32 and an Mw of 846 000. This polymer was accompanied by a smaller galactoglucan (44%), with an Mw of 6.5 × 104. The latter group (17%), retained by the gel, was further described as a HMW pectin heterogeneous group, with, respectively, 3.1 × 105 and 1.3 × 105. Despite the presence of HMW arabinoxylans, the investigation of rheological flow sweep at the concentration of 2% (w/v) has shown a slight shear thinning behavior with a small zero-rate viscosity at 9.6 Pa·s