Europe’s self-defence: Tous pour un et un pour tous? CEPS Commentary, 20 November 2015

When addressing the French Parliament following last week’s terrorist atrocities in Paris, French President François Hollande invoked Article 42(7) of the Treaty on the European Union. Never before has this EU’s ‘mutual assistance clause’ been activated by an EU member state. What does it provide and what are its practical implications

From self-doubt to self-assurance: The European External Action Service as the indispensable support for a geopolitical EU. CEPS Task Force Report 29 Jan 2021.

The rivalry and contestation of today’s world should be reason enough for the European Union to act as a cohesive force, if only to avoid being outmanoeuvred by major powers. Yet EU countries and institutions are still struggling to set aside their differences and focus on the common interest. The 10th anniversary of the European External Action Service is an opportune moment to take stock of its contribution to creating a more active, coherent and visible EU foreign policy. Despite its significant achievements, the Service still suffers from a lack of buy-in from member states and other parts of the EU administration. This study reappraises the EEAS’ actual and potential mission in the coming years, considering the dynamic ecosystem within which it functions. Distilling key lessons from the first decade of the Service’s operation, the report sets out 30 recommendations to address the identified shortcomings. It aims to assist the EEAS’ purpose of forging a distinctly European brand of diplomacy, by upgrading its operation to allow it more flexibility to think, propose and act, more agility to factor in a rapidly changing international landscape, and more determination to play a leading role. The Service could indeed make much more of its core assets, especially the integrated approach, the diversity of its in-house diplomatic expertise, a formidable network of delegations around the world, and a single intelligence analysis capacity, among others. In doing so it would better serve the common interests of the European Union and truly fulfil its objectives in external action. This report is the fruit of intense research cooperation between CEPS, SIEPS and the Friedrich Ebert Stiftung

The ‘special relationship’ between the EU and the EEA EFTA States and the free movement of persons in an extended area of freedom, security and justice - Case C-897/19 PPU, Ruska Federacija v. I.N., judgment of the CJEU (Grand Chamber) of 2 April 2020

Under embargo until: 2021-12-01acceptedVersio

Regulatory B Cells: An Exciting Target for Future Therapeutics in Transplantation.

International audience: Transplantation is the preferred treatment for most end-stage solid organ diseases. Despite potent immunosuppressive agents, chronic rejection remains a real problem in transplantation. For many years, the predominant immunological focus of research into transplant rejection has been T cells. The pillar of immunotherapy in clinical practice is T cell-directed, which efficiently prevents acute T cell-mediated allograft rejection. However, the root of late allograft failure is chronic rejection and the humoral arm of the immune response now emerges as an important factor in transplantation. Thus, the potential effects of Abs and B cell infiltrate on transplants have cast B cells as major actors in late graft rejection. Consequently, a number of recent drugs target either B cells or plasma cells. However, immunotherapies, such as the anti-CD20 B cell-depleting antibody, can generate deleterious effects on the transplant, likely due to the deletion of beneficial population. The positive contribution of regulatory B (Breg) cells or B10 cells has been reported in the case of transplantation, mainly in mice models and highlights the primordial role that some populations of B cells can play in graft tolerance. Yet, this regulatory aspect remains poorly characterized in clinical transplantation. Thus, total B cell depletion treatments should be avoided and novel approaches should be considered that manipulate the different B cell subsets. This article provides an overview of the current knowledge on the link between Breg cells and grafts, and reports a number of data advising Breg cells as a new target for future therapeutic approaches

Regulatory B Cells: An Exciting Target for Future Therapeutics in Transplantation.

International audience: Transplantation is the preferred treatment for most end-stage solid organ diseases. Despite potent immunosuppressive agents, chronic rejection remains a real problem in transplantation. For many years, the predominant immunological focus of research into transplant rejection has been T cells. The pillar of immunotherapy in clinical practice is T cell-directed, which efficiently prevents acute T cell-mediated allograft rejection. However, the root of late allograft failure is chronic rejection and the humoral arm of the immune response now emerges as an important factor in transplantation. Thus, the potential effects of Abs and B cell infiltrate on transplants have cast B cells as major actors in late graft rejection. Consequently, a number of recent drugs target either B cells or plasma cells. However, immunotherapies, such as the anti-CD20 B cell-depleting antibody, can generate deleterious effects on the transplant, likely due to the deletion of beneficial population. The positive contribution of regulatory B (Breg) cells or B10 cells has been reported in the case of transplantation, mainly in mice models and highlights the primordial role that some populations of B cells can play in graft tolerance. Yet, this regulatory aspect remains poorly characterized in clinical transplantation. Thus, total B cell depletion treatments should be avoided and novel approaches should be considered that manipulate the different B cell subsets. This article provides an overview of the current knowledge on the link between Breg cells and grafts, and reports a number of data advising Breg cells as a new target for future therapeutic approaches

Autoantibodies to Endothelial Cell Surface ATP Synthase, the Endogenous Receptor for Hsp60, Might Play a Pathogenic Role in Vasculatides

International audienceBACKGROUND: Heat shock protein (hsp) 60 that provides "danger signal" binds to the surface of resting endothelial cells (EC) but its receptor has not yet been characterized. In mitochondria, hsp60 specifically associates with adenosine triphosphate (ATP) synthase. We therefore examined the possible interaction between hsp60 and ATP synthase on EC surface. METHODOLOGY/PRINCIPAL FINDINGS: Using Far Western blot approach, co-immunoprecipitation studies and surface plasmon resonance analyses, we demonstrated that hsp60 binds to the β-subunit of ATP synthase. As a cell surface-expressed molecule, ATP synthase is potentially targeted by anti-EC-antibodies (AECAs) found in the sera of patients suffering vasculitides. Based on enzyme-linked immunosorbent assay and Western blotting techniques with F1-ATP synthase as substrate, we established the presence of anti-ATP synthase antibodies at higher frequency in patients with primary vasculitides (group I) compared with secondary vasculitides (group II). Anti-ATP synthase reactivity from group I patients was restricted to the β-subunit of ATP synthase, whereas those from group II was directed to the α-, β- and γ-subunits. Cell surface ATP synthase regulates intracellular pH (pHi). In low extracellular pH medium, we detected abnormal decreased of EC pHi in the presence of anti-ATP synthase antibodies, irrespective of their fine reactivities. Interestingly, soluble hsp60 abrogated the anti-ATP synthase-induced pHi down-regulation. CONCLUSIONS/SIGNIFICANCE: Our results indicate that ATP synthase is targeted by AECAs on the surface of EC that induce intracellular acidification. Such pathogenic effect in vasculitides can be modulated by hsp60 binding on ATP synthase which preserves ATP synthase activity

EEAS 2.0: draft recommendations for the 2013 EEAS Review

This document offers recommendations for the amendment of Council Decision 2010/427/EU establishing the organisation and functioning of the European External Action Service (hereinafter ‘EEAS Decision’). These recommendations have been distilled from discussions between academics and practitioners during a two-day workshop held at the European University Institute in March 2013 in the framework of the so-called ‘EEAS 2.0’ project. This research project is a collaboration between independent scholars brought together by SIEPS, the EUI and CEPS. In February 2013, the team published a legal commentary on the EEAS Decision, available on the websites of the participating research centres. The current paper and its recommendations should be read in the light thereof. In formulating the recommendations, attention has been paid to policy papers, non-papers and recommendations that have been initiated by EU institutions, member states, think tanks and academia, notably in the context of the on-going review. As such, we hope to be able to inform, in a precise and legal way, the discussions in preparation of the High Representative’s own report. The current paper is work in progress and will be revisited for publication after the summer, taking into account the High Representative’s report of July and feedback from other stakeholders The current paper sheds light on possible adjustments in the operation of the Decision/Service ‘à droit constant’, but also includes proposals that could be considered in the context of an amendment of the EEAS Decision. With regard to the latter, several levels of revision may be envisaged: (i) a mere toilettage (e.g. deleting out-dated provisions and securing terminological consistency), (ii) technical changes in the text without reopening the political discussion that predated the adoption of the Decision and (iii) a more ambitious revision that could require more extensive legal modifications of collateral secondary measures (e.g. Staff and/or Financial regulations), if not of the founding treaties