Impact de la loi Dodd-Frank sur le niveau de divulgation des agences de notation de crédit

La loi Dodd-Frank fut promulguée en 2010 par les États Unis en réponse à la crise financière de 2008. Elle a pour principale exigence l'amélioration de la transparence des agences de notation de crédit, tout particulièrement la transparence des agences ayant obtenu de la Security Exchange Commission, la SEC, le statut de Nationally Recognized Statistical Rating Organization, NRSRO. À notre connaissance, aucune étude n'a encore cherché à comprendre l'effet de la loi Dodd-Frank sur le comportement informationnel des agences de notation. Afin de pallier la situation, nous nous appuyons sur l'analyse des rapports produits annuellement auprès de la SEC par toute agence NRSRO, dans le but d'identifier toute amélioration de divulgation et de transparence, en conformité avec la nouvelle loi. Nous espérons ainsi être en mesure de déterminer l'impact informationnel de la nouvelle loi, c'est-à-dire son effet sur l'amélioration de la transparence des agences de notation de crédit. Étant donné l'indisponibilité de l'information pour toutes les agences NRSRO, l'étude s'est concentrée sur le cas de l'agence de crédit Moody's, assurant plus de 45% de l'ensemble des activités de notation. Elle est basée sur la théorie de la légitimité et sur la théorie institutionnelle et catégorise l'information produite annuellement auprès de la SEC et la classe selon des critères spécifiques élaborés en fonction des exigences relatives à la nouvelle loi. L'étude compare les informations divulguées par les agences avant l'adoption de la loi Dodd-Frank, à celles divulguées après, et conclut à des résultats mitigés, dépendamment de l'élément informationnel considéré.\ud ______________________________________________________________________________ \ud MOTS-CLÉS DE L’AUTEUR : Dodd-Frank, Sarbanes-Oxley, crise financière, agences de notation, divulgation, transparence

A novel mouse model based on intersectional genetics enables unambiguous in vivo discrimination between plasmacytoid and other dendritic cells and their comparative characterization

Abstract Plasmacytoid dendritic cells (pDC) were identified about 20 years ago, based on their unique ability to rapidly produce copious amounts of all subsets of type I and type III interferon (IFN-I/III) upon virus sensing, while being refractory to infection. Yet, the identity and physiological functions of pDC are still a matter of debate, in a large part due to their lack of specific expression of any single cell surface marker or gene that would allow to track them in tissues and to target them in vivo with high specificity and penetrance. Indeed, recent studies showed that previous methods that were used to identify or deplete pDC also targeted other cell types, including pDC-like cells and transitional DC (tDC) that were proposed to be responsible for all the antigen presentation ability previously attributed to steady state pDC. Hence, improving our understanding of the nature and in vivo choreography of pDC physiological functions requires the development of novel tools to unambiguously identify and track these cells, including in comparison to pDC-like cells and tDC. Here, we report successful generation of a pDC-reporter mouse model, by using an intersectional genetic strategy based on the unique co-expression of Siglech and Pacsin1 in pDC. This pDC-Tomato mouse strain allows specific ex vivo and in situ detection of pDC. Breeding them with Zbtb46 GFP mice allowed side-by-side purification and transcriptional profiling by single cell RNA sequencing of bona fide pDC, pDC-like cells and tDC, in comparison to type 1 and 2 conventional DC (cDC1 and cDC2), both at steady state and during a viral infection, revealing diverging activation patterns of pDC-like cells and tDC. Finally, by breeding pDC-Tomato mice with Ifnb1 EYFP mice, we determined the choreography of pDC recruitment to the micro-anatomical sites of viral replication in the spleen, with initially similar but later divergent behaviors of the pDC that engaged or not into IFN-I production. Our novel pDC-Tomato mouse model, and newly identified gene modules specific to combinations of DC types and activations states, will constitute valuable resources for a deeper understanding of the functional division of labor between DC types and its molecular regulation at homeostasis and during viral infections

Single-cell analysis of mouse plasmacytoid dendritic cells during an in vivo viral infection unravels their activation trajectory and their molecular regulation

17th International Congress of Immunology (IUIS), Beijing, PEOPLES R CHINA, OCT 19-23, 201

Single-cell analysis of mouse plasmacytoid dendritic cells during an in vivo viral infection unravels their activation trajectory and their molecular regulation

17th International Congress of Immunology (IUIS), Beijing, PEOPLES R CHINA, OCT 19-23, 201

Molecular dissection of plasmacytoid dendritic cell activation in vivo during a viral infection

International audiencePlasmacytoid dendritic cells (pDC) are the major source of type I interferons (IFN-I) during viral infections, in response to triggering of endosomal Toll-like receptors (TLRs) 7 or 9 by viral single-stranded RNA or unmethylated CpG DNA, respectively. Synthetic ligands have been used to disentangle the underlying signaling pathways. The adaptor protein AP3 is necessary to transport molecular complexes of TLRs, synthetic CpG DNA, and MyD88 into endosomal compartments allowing interferon regulatory factor 7 (IRF7) recruitment whose phosphorylation then initiates IFN-I production. High basal expression of IRF7 by pDC and its further enhancement by positive IFN-I feedback signaling appear to be necessary for robust cytokine production. In contrast, we show here that in vivo during mouse cytomegalovirus (MCMV) infection pDC produce high amounts of IFN-I downstream of the TLR9-to-MyD88-to-IRF7 signaling pathway without requiring IFN-I positive feedback, high IRF7 expression, or AP3-driven endosomal routing of TLRs. Hence, the current model of the molecular requirements for professional IFN-I production by pDC, established by using synthetic TLR ligands, does not strictly apply to a physiological viral infection

Novel mouse models based on intersectional genetics to identify and characterize plasmacytoid dendritic cells

Plasmacytoid dendritic cells (pDCs) are the main source of type I interferon (IFN-I) during viral infections. Their other functions are debated, due to a lack of tools to identify and target them in vivo without affecting pDC-like cells and transitional DCs (tDCs), which harbor overlapping phenotypes and transcriptomes but a higher efficacy for T cell activation. In the present report, we present a reporter mouse, pDC-Tom, designed through intersectional genetics based on unique Siglech and Pacsin1 coexpression in pDCs. The pDC-Tom mice specifically tagged pDCs and, on breeding with Zbtb46GFP mice, enabled transcriptomic profiling of all splenic DC types, unraveling diverging activation of pDC-like cells versus tDCs during a viral infection. The pDC-Tom mice also revealed initially similar but later divergent microanatomical relocation of splenic IFN+ versus IFN− pDCs during infection. The mouse models and specific gene modules we report here will be useful to delineate the physiological functions of pDCs versus other DC types

The activation trajectory of plasmacytoid dendritic cells in vivo during a viral infection

International audienc

The activation trajectory of plasmacytoid dendritic cells in vivo during a viral infection

International audiencePlasmacytoid dendritic cells (pDCs) are a major source of type I interferon (IFN-I). What other functions pDCs exert in vivo during viral infections is controversial, and more studies are needed to understand their orchestration. In the present study, we characterize in depth and link pDC activation states in animals infected by mouse cytomegalovirus by combining Ifnb1 reporter mice with flow cytometry, single-cell RNA sequencing, confocal microscopy and a cognate CD4 T cell activation assay. We show that IFN-I production and T cell activation were performed by the same pDC, but these occurred sequentially in time and in different micro-anatomical locations. In addition, we show that pDC commitment to IFN-I production was marked early on by their downregulation of leukemia inhibitory factor receptor and was promoted by cell-intrinsic tumor necrosis factor signaling. We propose a new model for how individual pDCs are endowed to exert different functions in vivo during a viral infection, in a manner tightly orchestrated in time and space