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Many countries choose policy objectives around their renewable energy expansion targets, such as efficiency and effectiveness. Due to the different nature and impact of those objectives, not all can be achieved simultaneously, so prioritising objectives is advisable. In this paper, we theoretically analyse the relationship between objectives and show that most European countries with renewable energy auctions in place have defined incoherent policy strategies in their respective renewable energy legislation. Based on these strategies, we analyse which objectives lead to the choice of which auction design elements conducting a qualitative comparative analysis. Considering 269 auction rounds from 20 European countries in the period 2011–2020, not all resulting choices of auction designs are in line with auction theory and existing literature’s findings on the relationship between objectives and auction design. Nevertheless, we show that on a country-level basis, most considered countries choose congruent auction designs, which either support all their (coherent) stated objectives or prioritise one or several of their incoherent objectives. For those countries with an incongruent auction design, we give recommendations on how to adapt their auction design depending on their exact choice of policy objectives.

After natalizumab (NAT) cessation, some multiple sclerosis (MS) patients experience a severe disease rebound. The rebound pathophysiology is still unclear; however, it has been linked to interleukin-17-producing T-helper (Th17) cells. We demonstrate that during NAT treatment, MCAM+CCR6+Th17 cells gradually acquire a pathogenic profile, including proinflammatory cytokine production, pathogenic transcriptional signatures, brain endothelial barrier impairment, and oligodendrocyte damage via induction of apoptotic pathways. This is accompanied by an increase in Th17 cell frequencies in the cerebrospinal fluid of NAT-treated patients. Notably, Th17 cells derived from NAT-treated patients, who later developed a disease rebound upon treatment cessation, displayed a distinct transcriptional pathogenicity profile associated with altered migratory properties. Accordingly, increased brain infiltration of patient Th17 cells was illustrated in a humanized mouse model and brain histology from a rebound patient. Therefore, peripheral blood-accumulated MCAM+CCR6+Th17 cells might be involved in rebound pathophysiology, and monitoring of changes in Th17 cell pathogenicity in patients before/during NAT treatment cessation might enable rebound risk assessment in the future.

Pericytes at the blood–brain barrier (BBB) are located between the tight endothelial cell layer of the blood vessels and astrocytic endfeet. They contribute to central nervous system (CNS) homeostasis by regulating BBB development and maintenance. Loss of pericytes results in increased numbers of infiltrating immune cells in the CNS in experimental autoimmune encephalomyelitis (EAE), the mouse model for multiple sclerosis (MS). However, little is known about their competence to modulate immune cell activation or function in CNS autoimmunity. To evaluate the capacity of pericytes to directly interact with T cells in an antigen-specific fashion and potentially (re)shape their function, we depleted major histocompatibility complex (MHC) class II from pericytes in a cell type-specific fashion and performed T cell-pericyte cocultures and EAE experiments. We found that pericytes present antigen in vitro to induce T cell activation and proliferation. In an adoptive transfer EAE experiment, pericyte-specific MHC II KO resulted in locally enhanced T cell infiltration in the CNS; even though, overall disease course of mice was not affected. Thus, pericytes may serve as non-professional antigen-presenting cells affecting states of T cell activation, thereby locally shaping lesion formation in CNS inflammation but without modulating disease severity.

A close interaction between gut immune responses and distant organ-specific autoimmunity including the CNS in multiple sclerosis has been established in recent years. This so-called gut–CNS axis can be shaped by dietary factors, either directly or via indirect modulation of the gut microbiome and its metabolites. Here, we report that dietary supplementation with conjugated linoleic acid, a mixture of linoleic acid isomers, ameliorates CNS autoimmunity in a spontaneous mouse model of multiple sclerosis, accompanied by an attenuation of intestinal barrier dysfunction and inflammation as well as an increase in intestinal myeloid-derived suppressor-like cells. Protective effects of dietary supplementation with conjugated linoleic acid were not abrogated upon microbiota eradication, indicating that the microbiome is dispensable for these conjugated linoleic acid-mediated effects. Instead, we observed a range of direct anti-inflammatory effects of conjugated linoleic acid on murine myeloid cells including an enhanced IL10 production and the capacity to suppress T-cell proliferation. Finally, in a human pilot study in patients with multiple sclerosis (n = 15, under first-line disease-modifying treatment), dietary conjugated linoleic acid-supplementation for 6 months significantly enhanced the anti-inflammatory profiles as well as functional signatures of circulating myeloid cells. Together, our results identify conjugated linoleic acid as a potent modulator of the gut–CNS axis by targeting myeloid cells in the intestine, which in turn control encephalitogenic T-cell responses., Fleck et al. report that dietary supplementation with conjugated linoleic acid elicits anti-inflammatory and suppressive myeloid cell responses in the intestine, resulting in amelioration of CNS autoimmunity in mice and a beneficial modulation of myeloid cell responses in patients with relapsing-remitting multiple sclerosis.

An increasing number of countries use auctions to allocate support for renewable energies. One major objective of policymakers when designing auctions is support cost efficiency, i.e., achieving low awarded prices. Based on a holistic database with auction outcomes from Europe covering the years 2012-2020, we conduct a fixed effects panel data regression to assess the effects of several auction design elements on the awarded prices. According to our results, policymakers aiming for low prices in renewable energy auctions should avoid restricting auctions to small-scale projects, implement ceiling prices, and ensure high levels of competition. Multi-technology auctions can also lead to higher efficiency, while quotas should be avoided. While PV tends to achieve lower prices in auctions restricted to small-scale projects, onshore wind performs better in auctions open to large-scale projects. Feed-in premia, multi-criteria auctions and allowing bidders to deviate from their awarded project capacity show no significant impact. The introduction of financial prequalification requirements and the length of the realisation period should be chosen carefully, as their effects are interrelated. While our results for individual design elements are largely in line with existing literature, we are able to produce new insights on the interdependencies between various auction design elements.

Background The nuclear receptor farnesoid-X-receptor (FXR; NR1H4) is expressed not only in the liver, gut, kidney and adipose tissue but also in the immune cells. FXR has been shown to confer protection in several animal models of inflammation, including experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). FXR agonists are currently tested in clinical trials for treatment of human metabolic diseases. The beneficial effect of FXR agonists in EAE suggests that FXR might represent a potential target in inflammatory-demyelinating CNS diseases, such as MS. In MS, oligodendrocytes not only undergo cell death but also contribute to remyelination. This repair mechanism is impaired due to a differentiation block of oligodendroglial progenitor cells. Activation of other nuclear receptors that heterodimerize with FXR promote oligodendroglial differentiation. Therefore, we wanted to address the functional relevance of FXR for glial cells, especially for oligodendroglial differentiation. Methods We isolated primary murine oligodendrocytes from FXR-deficient (FXR Ko) and wild-type (WT) mice and determined the effect of FXR deficiency and activation on oligodendroglial differentiation by analysing markers of oligodendroglial progenitor cells (OPCs) and mature oligodendrocytes (OLs) using qRT-PCR and immunocytochemistry. Additionally, we determined whether FXR activation modulates the pro-inflammatory profile of astrocytes or microglia and whether this may subsequently modulate oligodendroglial differentiation. These in vitro studies were complemented by histological analyses of oligodendrocytes in FXR Ko mice. Results FXR is expressed by OPCs and mature oligodendrocytes. However, lack of FXR did not affect oligodendroglial differentiation in vitro or in vivo. Furthermore, activation of FXR using the synthetic agonist GW4064 did not affect oligodendroglial differentiation, remyelination in an ex vivo model or the expression of pro-inflammatory molecules in astrocytes or microglia. Concordantly, no effects of supernatants from macrophages cultured in the presence of GW4064 were observed regarding a possible indirect impact on oligodendroglial differentiation. Conclusions Our data suggest that FXR is dispensable for oligodendroglial differentiation and that FXR agonists, such as GW4064, represent a potential therapeutic approach for MS which specifically targets peripheral immune cells including macrophages but not brain-resident cells, such as oligodendrocytes, astrocytes or microglia. Electronic supplementary material The online version of this article (doi:10.1186/s12974-017-0833-6) contains supplementary material, which is available to authorized users.

In the last decade the role of environmental factors as modulators of disease activity and progression has received increasing attention. In contrast to classical environmental modulators such as exposure to sun-light or fine dust pollution, nutrition is an ideal tool for a personalized human intervention. Various studies demonstrate a key role of dietary factors in autoimmune diseases including Inflammatory Bowel Disease (IBD), rheumatoid arthritis or inflammatory central nervous system (CNS) diseases such as Multiple Sclerosis (MS). In this review we discuss the connection between diet and inflammatory processes via the gut–CNS-axis. This axis describes a bi-directional communication system and comprises neuronal signaling, neuroendocrine pathways and modulation of immune responses. Therefore, the gut–CNS-axis represents an emerging target to modify CNS inflammatory activity ultimately opening new avenues for complementary and adjunctive treatment of autoimmune diseases such as MS.

Innate immune responses by myeloid cells decisively contribute to perpetuation of central nervous system (CNS) autoimmunity and their pharmacologic modulation represents a promising strategy to prevent disease progression in Multiple Sclerosis (MS). Based on our observation that peripheral immune cells from relapsing-remitting and primary progressive MS patients exhibited strongly decreased levels of the bile acid receptor FXR (farnesoid-X-receptor, NR1H4), we evaluated its potential relevance as therapeutic target for control of established CNS autoimmunity. Pharmacological FXR activation promoted generation of anti-inflammatory macrophages characterized by arginase-1, increased IL-10 production, and suppression of T cell responses. In mice, FXR activation ameliorated CNS autoimmunity in an IL-10-dependent fashion and even suppressed advanced clinical disease upon therapeutic administration. In analogy to rodents, pharmacological FXR activation in human monocytes from healthy controls and MS patients induced an anti-inflammatory phenotype with suppressive properties including control of effector T cell proliferation. We therefore, propose an important role of FXR in control of T cell-mediated autoimmunity by promoting anti-inflammatory macrophage responses.

Background The recent identification of several mutations in PFN1, a protein involved in actin dynamics, strengthens the hypothesis that pathology of amyotrophic lateral sclerosis is linked to cytoskeletal defects. Impaired actin binding is a common denominator of several PFN1 mutations associated with amyotrophic lateral sclerosis, although further mechanisms may also contribute to the death of motor neurons. In this study we examine the actin binding properties of PFN1 carrying the causal T109M mutation and its effects on the actin cytoskeleton. Methods Actin binding of PFN1 T109M was examined by co-immunoprecipitation experiments, a split luciferase complementation assay and a pulldown assay with recombinant PFN1. The actin cytoskeleton was investigated by fluorescence microscopy and by ultracentrifuge separation of globular and filamentous actin fractions followed by Western blotting. Results Using different technical approaches we show that PFN1 T109M displays unaltered actin binding. Furthermore we show that the actin cytoskeleton is not affected by PFN1 carrying the T109M mutation. Conclusion Our data suggest that actin independent mechanisms contribute to the pathogenicity of PFN1 T109M and possibly other PFN1 mutations.