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  1. Article ; Online: How Microbiota-Derived Metabolites Link the Gut to the Brain during Neuroinflammation

    Jessica Rebeaud / Benjamin Peter / Caroline Pot

    International Journal of Molecular Sciences, Vol 23, Iss 10128, p

    2022  Volume 10128

    Abstract: Microbiota-derived metabolites are important molecules connecting the gut to the brain. Over the last decade, several studies have highlighted the importance of gut-derived metabolites in the development of multiple sclerosis (MS). Indeed, microbiota- ... ...

    Abstract Microbiota-derived metabolites are important molecules connecting the gut to the brain. Over the last decade, several studies have highlighted the importance of gut-derived metabolites in the development of multiple sclerosis (MS). Indeed, microbiota-derived metabolites modulate the immune system and affect demyelination. Here, we discuss the current knowledge about microbiota-derived metabolites implications in MS and in different mouse models of neuroinflammation. We focus on the main families of microbial metabolites that play a role during neuroinflammation. A better understanding of the role of those metabolites may lead to new therapeutical avenues to treat neuroinflammatory diseases targeting the gut–brain axis.
    Keywords neuroinflammation ; multiple sclerosis ; experimental autoimmune encephalomyelitis ; gut–brain axis ; microbiota-derived metabolites ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Language English
    Publishing date 2022-09-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Oxysterols in Autoimmunity

    Donovan Duc / Solenne Vigne / Caroline Pot

    International Journal of Molecular Sciences, Vol 20, Iss 18, p

    2019  Volume 4522

    Abstract: Cholesterol is a member of the sterol family that plays essential roles in biological processes, including cell membrane stability and myelin formation. Cholesterol can be metabolized into several molecules including bile acids, hormones, and oxysterols. ...

    Abstract Cholesterol is a member of the sterol family that plays essential roles in biological processes, including cell membrane stability and myelin formation. Cholesterol can be metabolized into several molecules including bile acids, hormones, and oxysterols. Studies from the last few decades have demonstrated that oxysterols are not only active metabolites but are further involved in the modulation of immune responses. Liver X Receptors (LXRs), nuclear receptors for oxysterols, are important for cholesterol homeostasis and regulation of inflammatory response but are still poorly characterized during autoimmune diseases. Here we review the current knowledge about the role of oxysterols during autoimmune conditions and focus on the implication of LXR-dependent and LXR-independent pathways. We further highlight the importance of these pathways in particular during central nervous system (CNS) autoimmunity and inflammatory bowel diseases (IBD) in both experimental models and human studies. Finally, we discuss our vision about future applications and research on oxysterols related to autoimmunity.
    Keywords Liver X receptors ; oxysterols ; Ebi2 ; ROR ; Ch25h ; autoimmunity ; multiple sclerosis ; inflammatory bowel disease ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 571
    Language English
    Publishing date 2019-09-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Disrupting Myelin-Specific Th17 Cell Gut Homing Confers Protection in an Adoptive Transfer Experimental Autoimmune Encephalomyelitis

    Donovan Duc / Solenne Vigne / Jeremiah Bernier-Latmani / Yannick Yersin / Florian Ruiz / Nadia Gaïa / Stefano Leo / Vladimir Lazarevic / Jacques Schrenzel / Tatiana V. Petrova / Caroline Pot

    Cell Reports, Vol 29, Iss 2, Pp 378-390.e

    2019  Volume 4

    Abstract: Summary: Multiple sclerosis (MS) is a common autoimmune disease of the CNS. Although an association between MS and inflammatory bowel diseases is observed, the link connecting intestinal immune responses and neuroinflammation remains unclear. Here we ... ...

    Abstract Summary: Multiple sclerosis (MS) is a common autoimmune disease of the CNS. Although an association between MS and inflammatory bowel diseases is observed, the link connecting intestinal immune responses and neuroinflammation remains unclear. Here we show that encephalitogenic Th17 cells infiltrate the colonic lamina propria before neurological symptom development in two murine MS models, active and adoptive transfer experimental autoimmune encephalomyelitis (EAE). Specifically targeting Th17 cell intestinal homing by blocking the α4β7-integrin and its ligand MAdCAM-1 pathway impairs T cell migration to the large intestine and dampens EAE severity in the Th17 cell adoptive transfer model. Mechanistically, myelin-specific Th17 cells proliferate in the colon and affect gut microbiota composition. The beneficial effect of blocking the α4β7-integrin and its ligand MAdCAM-1 pathway on EAE is interdependent with gut microbiota. Those results show that disrupting myelin-specific Th17 cell trafficking to the large intestine harnesses neuroinflammation and suggests that the gut environment and microbiota catalyze the encephalitogenic properties of Th17 cells. : Duc et al. show that Th17-polarized myelin-specific (TCRMOG 2D2) CD4+ T cells migrate to the colon before the development of neuroinflammation. Encephalitogenic Th17 cells further change intestinal microbiome composition. Blocking encephalitogenic Th17 cell entry into the colon or treatment with antibiotics ameliorates EAE severity. Keywords: multiple sclerosis, EAE, Th17 cells, trafficking, α4β7, integrin, MAdCAM-1, intestinal microbiome, gut-brain axis, neuroinflammation
    Keywords Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2019-10-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: The Swiss Multiple Sclerosis Cohort-Study (SMSC)

    Giulio Disanto / Pascal Benkert / Johannes Lorscheider / Stefanie Mueller / Jochen Vehoff / Chiara Zecca / Simon Ramseier / Lutz Achtnichts / Oliver Findling / Krassen Nedeltchev / Ernst-Wilhelm Radue / Till Sprenger / Christoph Stippich / Tobias Derfuss / Jean-François Louvion / Christian P Kamm / Heinrich P Mattle / Christoph Lotter / Renaud Du Pasquier /
    Myriam Schluep / Caroline Pot / Patrice H Lalive / Özgür Yaldizli / Claudio Gobbi / Ludwig Kappos / Jens Kuhle / SMSC Scientific Board

    PLoS ONE, Vol 11, Iss 3, p e

    A Prospective Swiss Wide Investigation of Key Phases in Disease Evolution and New Treatment Options.

    2016  Volume 0152347

    Abstract: The mechanisms leading to disability and the long-term efficacy and safety of disease modifying drugs (DMDs) in multiple sclerosis (MS) are unclear. We aimed at building a prospective cohort of MS patients with standardized collection of demographic, ... ...

    Abstract The mechanisms leading to disability and the long-term efficacy and safety of disease modifying drugs (DMDs) in multiple sclerosis (MS) are unclear. We aimed at building a prospective cohort of MS patients with standardized collection of demographic, clinical, MRI data and body fluids that can be used to develop prognostic indicators and biomarkers of disease evolution and therapeutic response. The Swiss MS Cohort (SMSC) is a prospective observational study performed across seven Swiss MS centers including patients with MS, clinically isolated syndrome (CIS), radiologically isolated syndrome or neuromyelitis optica. Neurological and radiological assessments and biological samples are collected every 6-12 months. We recruited 872 patients (clinically isolated syndrome [CIS] 5.5%, relapsing-remitting MS [RRMS] 85.8%, primary progressive MS [PPMS] 3.5%, secondary progressive MS [SPMS] 5.2%) between June 2012 and July 2015. We performed 2,286 visits (median follow-up 398 days) and collected 2,274 serum, plasma and blood samples, 152 cerebrospinal fluid samples and 1,276 brain MRI scans. 158 relapses occurred and expanded disability status scale (EDSS) scores increased in PPMS, SPMS and RRMS patients experiencing relapses. Most RRMS patients were treated with fingolimod (33.4%), natalizumab (24.5%) or injectable DMDs (13.6%). The SMSC will provide relevant information regarding DMDs efficacy and safety and will serve as a comprehensive infrastructure available for nested research projects.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2016-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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