T Follicular Helper Cells in Autoimmune Disorders

T follicular helper (Tfh) cells are a distinct subset of CD4+ T lymphocytes, specialized in B cell help and in regulation of antibody responses. They are required for the generation of germinal center reactions, where selection of high affinity antibody producing B cells and development of memory B cells occur. Owing to the fundamental role of Tfh cells in adaptive immunity, the stringent control of their production and function is critically important, both for the induction of an optimal humoral response against thymus-dependent antigens but also for the prevention of self-reactivity. Indeed, deregulation of Tfh activities can contribute to a pathogenic autoantibody production and can play an important role in the promotion of autoimmune diseases. In the present review, we briefly introduce the molecular factors involved in Tfh cell formation in the context of a normal immune response, as well as markers associated with their identification (transcription factor, surface marker expression, and cytokine production). We then consider in detail the role of Tfh cells in the pathogenesis of a broad range of autoimmune diseases, with a special focus on systemic lupus erythematosus and rheumatoid arthritis, as well as on the other autoimmune/inflammatory disorders. We summarize the observed alterations in Tfh numbers, activation state, and circulating subset distribution during autoimmune and some other inflammatory disorders. In addition, central role of interleukin-21, major cytokine produced by Tfh cells, is discussed, as well as the involvement of follicular regulatory T cells, which share characteristics with both Tfh and regulatory T cells

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Régulations de la diffusion latérale et du nombre de récepteurs de la glycine aux synapses

La régulation du nombre de récepteurs de la glycine (RGly) aux synapses est fondamentale pour l efficacité de la transmission inhibitrice et le contrôle de l excitabilité neuronale dans la moelle épinière. L objectif de cette thèse a été d étudier les régulations de la diffusion-capture et de l accumulation des RGly aux synapses. J ai montré que le cytosquelette régule rapidement le nombre de RGly aux synapses en contrôlant leur diffusion latérale et leur temps de résidence aux synapses. J ai ensuite montré que les intégrines, des molécules d adhérence qui interagissent avec la matrice extracellulaire et des facteurs neuronaux et gliaux, déterminent les quantités synaptiques de RGly et de sa protéine associée, la géphyrine. Les integrines 1 et 3 ont des actions opposées aux synapses et dialoguent par l intermédiaire de la kinase II calcium/calmoduline-dépendante (CaMKII). Les résultats permettent de postuler que la CaMKII phosphoryle la géphyrine, ce que qui affecte la capture des RGly aux synapses. Ceci fournit un mécanisme pour ajuster les échanges de molécules postsynaptiques et l efficacité de la transmission glycinergique.PARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Équipe mobile de crise intrafamiliale : un dispositif d’évaluation et d’accès aux soins pour les enfants exposés aux violences conjugales en partenariat avec la Gendarmerie nationale

Les enfants exposés aux violences conjugales constituent une population vulnérable en possible souffrance psychique et à risque de développer ultérieurement des conduites d’agression ou de victimisation. La difficulté pour les équipes soignantes est de pouvoir accéder précocement à ces enfants car la plupart des familles concernées ne viennent pas consulter spontanément. Il est donc important d’aller à la rencontre des enfants exposés aux violences conjugales et de leurs familles grâce à des équipes mobiles de pédopsychiatrie pour évaluer les possibles difficultés psychiques. Ces équipes mobiles sont alertées par des professionnels de première ligne qui ont connaissance de ces situations (comme par exemple, les gendarmes, policiers, travailleurs sociaux, pédiatres, médecins généralistes, professionnels de l’Éducation nationale, etc.). L’efficacité de l’accès aux soins psychiques pour ces enfants dépend de la réactivité de la prise en charge (dans les 72 heures qui suivent l’intervention des professionnels de première ligne, ici la Gendarmerie nationale) et de la nécessité de pouvoir se déplacer au domicile de ces familles (les premiers rendez-vous ont lieu, à la demande des parents, tout d’abord chez eux)

L'impartialité de l'expert. Pourquoi ? Comment ? Quelles en sont les garanties ?

Table ronde, Archives Nationale

Emerging Mechanisms Underlying Dynamics of GABAergic Synapses

Inhibitory circuits are diverse, yet with a poorly understood cell biology. Functional characterization of distinct inhibitory neuron subtypes has not been sufficient to explain how GABAergic neurotransmission sculpts principal cell activity in a relevant fashion. Our Mini-Symposium brings together several emerging mechanisms that modulate GABAergic neurotransmission dynamically from either the presynaptic or the postsynaptic site. The first two talks discuss novel developmental and neuronal subtype-specific contributions to the excitatory/inhibitory balance and circuit maturation. The next three talks examine how interactions between cellular pathways, lateral diffusion of proteins between synapses, and chloride transporter function at excitatory and inhibitory synapses and facilitate inhibitory synapse adaptations. Finally, we address functional differences within GABAergic interneurons to highlight the importance of diverse, flexible, and versatile inputs that shape network function. Together, the selection of topics demonstrates how developmental and activity-dependent mechanisms coordinate inhibition in relation to the excitatory inputs and vice versa