Mutations in STAT3 and IL12RB1 impair the development of human IL-17–producing T cells

The cytokines controlling the development of human interleukin (IL) 17–producing T helper cells in vitro have been difficult to identify. We addressed the question of the development of human IL-17–producing T helper cells in vivo by quantifying the production and secretion of IL-17 by fresh T cells ex vivo, and by T cell blasts expanded in vitro from patients with particular genetic traits affecting transforming growth factor (TGF) β, IL-1, IL-6, or IL-23 responses. Activating mutations in TGFB1, TGFBR1, and TGFBR2 (Camurati-Engelmann disease and Marfan-like syndromes) and loss-of-function mutations in IRAK4 and MYD88 (Mendelian predisposition to pyogenic bacterial infections) had no detectable impact. In contrast, dominant-negative mutations in STAT3 (autosomal-dominant hyperimmunoglobulin E syndrome) and, to a lesser extent, null mutations in IL12B and IL12RB1 (Mendelian susceptibility to mycobacterial diseases) impaired the development of IL-17–producing T cells. These data suggest that IL-12Rβ1– and STAT-3–dependent signals play a key role in the differentiation and/or expansion of human IL-17–producing T cell populations in vivo

Mutations in STAT3 and IL12RB1 impair the development of human IL-17 producing T cells

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François Hollande’s victory is a very “normal” one for France’s left

The Monday morning edition of the French left magazine Libération featured a triumphant François Hollande alongside the headline “Normal!” to the bewilderment of many journalists outside France. Catherine Fieschi argues that “Normal!” perfectly captures the feeling of the left in France that Hollande’s victory does not mark a revolution in French politics, and reflects their feelings that he is more than capable of a competent and quietly confident presidency

Marine Le Pen will not capture more than 15 per cent of the vote despite her efforts to transform Front National into a less radical populist party

How many voters will support Front National candidate Marine Le Pen in the upcoming French presidential elections? Catherine Fieschi argues that despite Le Pen’s efforts to transform the Front National into a less radical right-wing party her campaign has reached its limits, and that she will struggle to capture more than 15 per cent of the vote

The French Fifth Republic and populism : a neo-institutional analysis of the Front national

The aim of the thesis is to offer an explanation for the emergence and success of the French political party the Front national. The project uses theories of political opportunity structures, neo-institutionalist approaches and a theory of ideological morphology to argue that institutions and ideologies have particular links to one another. This, in turn, leads to the argument that the FN's success can be attributed to the relationships between the institutions of the Fifth Republic on the one hand and fascist ideology in France on the other. It is argued that the gradual presidentialisation of French politics from 1958 onward reconciles two contradictory drives in French politics (the party drive and the rally drive), this reconciliation of the two drives and the institutionalisation of the rally drive grants renewed legitimacy to populist ideas in France. It is also argued that, given the component concepts of fascism as an ideology (its ideological morphology) and the links between ideologies and the contexts (institutional, social, political) in which they emerge, institutional pressures such as those generated by the Fifth Republic and its subsequent presidentialisation accounts for a mutation of French proto-fascism into a type of populist ideology. The FN's modification of its fascist ideology and conversion to an overt form of populism is depicted and analysed as a case study of a party's adaptation to, and exploitation of, the new structures of political opportunity created by the Fifth Republic; one in which populist ideas were more likely than fascist ones to lead to a measure of political success given the institutionalisation of a form of hitherto marginalised rally politics

"Capitalism, consensus, and the electoral successes of the far right"

The electoral success of Jean-Marie Le Pen in France and (the late) Pim Formyn in the Netherlands has sparked immediate speculation that ‘the right' is coming back into vogue in Europe. Such speculation assumes that the right-left dichotomy is important to understanding the success of groups like the Front National or the List Pim Fortuyn. We disagree. Using examples from across Europe, we argue that these groups are more characteristically populist than right-wing; that their stance on the structure of political participation is more important to their success than the position they take on distributive concerns; and that programmatic inconsistency is less critical than performance contradiction to their survival in power. Our argument is only slightly at odds with the existing literature, but even this slight change of emphasis- from policy or distributive outcomes to political or participatory process- can offer substantial analytic rewards. By focusing attention on the process elements in populist political programs we can not only anticipate the fare of those movements, but also shed light on the larger political systems within which they operate

How can the green energy transition succeed without harming regional cohesion in Europe?

This contribution was delivered on 23 May 2024 on the occasion of the hybrid 2024 edition of EUI State of the UnionThe latest research by Bertelsmann Stiftung on the EU economy comes to a surprising conclusion: Less-developed, rural regions in the EU could gain significantly in economic prosperity from a transition to renewable energy, while urban areas with high energy demands could face setbacks. In short, it’s well worth it for rural regions to pursue a renewable energy overhaul although their support is currently rather limited, while urban areas with high support for green policies could face future financial and political hurdles due to rising costs and political “greenlash.” This panel will grapple with the implications of these findings for policymakers, businesses and consumers and address questions like: - How can policymakers ensure buy-in from rural regions by highlighting these benefits? And what can be done to forestall waning support for green energy policies in urban areas? - How can rural and urban regions work together to leverage the strengths of each to meet the needs of the other? What can be done to end up with a mutually beneficiary outcome? - What synergies can be leveraged between the EU’s cohesion policy and energy policy? Can cohesion policy support energy policy goals

Human IgA binds a diverse array of commensal bacteria.

In humans, several grams of IgA are secreted every day in the intestinal lumen. While only one IgA isotype exists in mice, humans secrete IgA1 and IgA2, whose respective relations with the microbiota remain elusive. We compared the binding patterns of both polyclonal IgA subclasses to commensals and glycan arrays and determined the reactivity profile of native human monoclonal IgA antibodies. While most commensals are dually targeted by IgA1 and IgA2 in the small intestine, IgA1+IgA2+ and IgA1-IgA2+ bacteria coexist in the colon lumen, where Bacteroidetes is preferentially targeted by IgA2. We also observed that galactose-α terminated glycans are almost exclusively recognized by IgA2. Although bearing signs of affinity maturation, gut-derived IgA monoclonal antibodies are cross-reactive in the sense that they bind to multiple bacterial targets. Private anticarbohydrate-binding patterns, observed at clonal level as well, could explain these apparently opposing features of IgA, being at the same time cross-reactive and selective in its interactions with the microbiota

Low-Valent Calix[4]arene Glycoconjugates Based on Hydroxamic Acid Bearing Linkers as Potent Inhibitors in a Model of Ebola Virus Cis-Infection and HCMV-gB-Recombinant Glycoprotein Interaction with MDDC Cells by Blocking DC-SIGN

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