25 research outputs found

    Enlightening human B-cell diversity.

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    Type I interferon regulates the survival and functionality of B cells in rainbow trout

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    This work was supported by the European Research Council (ERC Consolidator Grant No. 2016 725061 TEMUBLYM), by the Spanish Ministry of Science, Innovation and Universities (project AGL2017-85494-C2-1-R) and by the Comunidad de Madrid (Grant No. 2016-T1/BIO-1672).Peer reviewedPublisher PD

    Effects of golimumab and ustekinumab on circulating dendritic cell migratory capacity in inflammatory bowel disease

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    Inflammatory bowel disease (IBD) is a chronic condition which includes ulcerative colitis (UC) and Crohn’s disease (CD), the origins of which are not yet fully understood. Both conditions involve an exacerbated immune response in the intestinal tract, leading to tissue inflammation. Dendritic cells (DCs) are antigen-presenting cells crucial for maintaining tolerance in the gastrointestinal mucosa. Previous research has indicated that DC recruitment to the intestinal mucosa is more pronounced in individuals with IBD, but the specific mechanisms governing this migration remain unclear. This study aimed to assess the expression of various homing markers and the migratory abilities of circulating DC subsets in response to intestinal chemotactic signals. Additionally, this study examined how golimumab and ustekinumab impact these characteristics in individuals with IBD compared to healthy controls. The findings revealed that a particular subset of DCs known as type 2 conventional DCs (cDC2) displayed a more pronounced migratory profile compared to other DC subsets. Furthermore, the study observed that golimumab and ustekinumab had varying effects on the migratory profile of cDC1 in individuals with CD and UC. While CCL2 did not exert a chemoattractant effect on DC subsets in this patient cohort, treatment with golimumab and ustekinumab enhanced their migratory capacity towards CCL2 and CCL25 while reducing their migration towards MadCam1. In conclusion, this study highlights that cDC2 exhibits a heightened migratory profile towards the gastrointestinal mucosa compared to other DC subsets. This finding could be explored further for the development of new diagnostic biomarkers or the identification of potential immunomodulatory targets in the context of IB

    Differential effects of Anti-TNFα and Anti-α4β7 drugs on circulating dendritic cells migratory capacity in inflammatory bowel disease

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    Inflammatory bowel disease (IBD) is an idiopathic and chronic disorder that includes ulcerative colitis (UC) and Crohn’s disease (CD). Both diseases show an uncontrolled intestinal immune response that generates tissue inflammation. Dendritic cells (DCs) are antigen-presenting cells that play a key role in tolerance maintenance in the gastrointestinal mucosa. Although it has been reported that DC recruitment by the intestinal mucosa is more prominent in IBD patients, the specific mechanisms governing this migration are currently unknown. In this study, the expression of several homing markers and the migratory profile of circulating DC subsets towards intestinal chemo-attractants were evaluated and the effect of biological drugs with different mechanisms of action, such as anti-TNFα or anti-integrin α4β7 (vedolizumab), on this mechanism in healthy controls (HCs) and IBD patients was also assessed. Our results revealed that type 2 conventional DCs (cDC2) express differential homing marker profiles in UC and CD patients compared to HCs. Indeed, integrin β7 was differentially modulated by vedolizumab in CD and UC. Additionally, although CCL2 displayed a chemo-attractant effect over cDC2, while biological therapies did not modulate the expression of the homing markers, we paradoxically found that anti-TNF-treated cDC2 increased their migratory capacity towards CCL2 in HCs and IBD. Our results therefore suggest a key role for cDC2 migration towards the intestinal mucosa in IBD, something that could be explored in order to develop novel diagnostic biomarkers or to unravel new immunomodulatory targets in IBD.This study has been funded through the Instituto de Salud Carlos III (Sara Borrell fellowships, CD17/00014; CD21/00014), Asociación Española de Gastroenterología (Beca del Grupo Joven), Programa Estratégico Instituto de Biología y Genética Molecular (IBGM Junta de Castilla y León. Ref. CCVC8485), Plan Nacional (PID2019-104218RB-I00) from the Spanish Government, Janssen and MSD

    CD38 Defines a Subset of B Cells in Rainbow Trout Kidney With High IgM Secreting Capacities

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    Funding Information: This work was supported by the European Research Council (ERC Consolidator Grant 2016 725061 TEMUBLYM) and by the Comunidad de Madrid (grant 2016-T1/BIO-1672).Peer reviewedPublisher PD

    Long non-coding RNA signatures in the Ileum and Colon of Crohn’s disease patients and effect of Anti-TNF-α treatment on their modulation

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    Biological therapies only benefit one-third of patients with Crohn’s disease (CD). For this reason, a deeper understanding of the mechanisms by which biologics elicit their effect on intestinal mucosa is needed. Increasing evidence points toward the involvement of long noncoding RNAs (lncRNAs) in the pathogenesis of CD, although their role remains poorly studied. We aimed to characterize lncRNA profiles in the ileum and colon from CD patients and evaluate the effect of anti-TNF-α treatment on their transcription. Terminal ileum and left colon samples from 30 patients (active CD = 10, quiescent CD = 10, and healthy controls (HCs) = 10) were collected for RNA-seq. The patients were classified according to endoscopic activity. Furthermore, biopsies were cultured with infliximab, and their transcriptome was determined by Illumina gene expression array. A total of 678 differentially expressed lncRNAs between the terminal ileum and left colon were identified in HCs, 438 in patients with quiescent CD, and 468 in patients with active CD. Additionally, we identified three new lncRNAs in the ileum associated with CD activity. No differences were observed when comparing the effect of infliximab according to intestinal location, presence of disease (CD vs. HC), and activity (active vs. quiescent). The expression profiles of lncRNAs are associated with the location of intestinal tissue, being very different in the ileum and colon. The presence of CD and disease activity are associated with the differential expression of lncRNAs. No modulatory effect of infliximab has been observed in the lncRNA transcriptom

    Reformulando el tratamiento procesal de las víctimas de violencia sexual en procesos penales

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    Esta obra presenta las investigaciones desarrolladas a lo largo del proyecto europeo de investigación, financiado por el Programa de Justicia de la Union Europea (2014-2020): “RE-TREAT: Reshaping treatment approaches towards victims of sexual crimes within criminal proceedings”. Los objetivos perseguidos por este proyecto de investigación son, entre otros, el análisis de las barreras, recursos y prácticas nocivas en el tratamiento de las víctimas de delitos sexuales a lo largo de las diversas fases del proceso penal, identificación de mejores prácticas en este ámbito que pueden ser aplicadas por los operadores jurídicos, o bien, la sensibilización de los actores que abordan este fenómeno. Se presentan en el primer Capítulo los obstáculos que enfrentan las víctimas de delitos sexuales en las diversas etapas del proceso penal español, se describen los estándares prácticos para profesionales del sistema de justicia que trabajan con víctimas de violencia sexual en el Capítulo II de la obra. En el Capítulo III se incluyen recomendaciones políticas que permiten garantizar un mejor tratamiento hacia las víctimas de violencia sexual por parte del sistema de justicia en España y en el Capítulo IV el informe comparativo de la situación con Grecia e Italia.Esta obra presenta las investigaciones desarrolladas a lo largo del proyecto europeo de investigación, financiado por el Programa de Justicia de la Union Europea (2014-2020): “RE-TREAT: Reshaping treatment approaches towards victims of sexual crimes within criminal proceedings”Financed by The European Union Justice Program (2014-2020). RE-TREAT: Reshaping treatment approaches towards victims of sexual violence within criminal proceedings. JUST-JACC-AG-2019 - 878566 - RETREATObstáculos que enfrentan las víctimas de delito sexual en las etapas del proceso penal / Helena Soleto, Sabela Oubiña Barbolla, Jessica Jullien de Asís, Aurea Grané Chávez, Margarita Diges Junco, Candela Galán González, Nieves Pérez-Mata, Anna Fiodorova, Federico González Barrera, Iván Navarro Papic, Rosa Gómez de Liaño, Raquel López Jiménez, Daniel Rodríguez Horcajo, Soledad Torrecuadrada García Lozano, Ignacio de Torres Guajardo, Belén Hernández Moura, Emiliano Carretero Morales, Irene de Lamo Velado, Rocío Zafra Espinosa de los Monteros, Cristina Ruiz López, Miriam Peláez Devesa (pp. 7-92). -- Guía para profesionales de la justicia que trabajan con mujeres víctimas de violencia sexual / Monique Anderson, Evelien Claes (pp. 93-116). -- Recomendaciones políticas / Monique Anderson, Evelien Claes, Anna Fiodorova, Helena Soleto (p. 117-165). -- Estudio comparativo sobre tratamiento procesal a víctimas de violencia sexual en España, Grecia e Italia / Sabela Oubiña Barbolla, Helena Soleto Muñoz, Nieves Pérez-Mata, Daniel Rodríguez Horcajo, Margarita Diges Junco, Miriam Peláez Devesa, Jessica Jullien de Asís, Aurea Grané, Candela Galán González, Manuel Cancio Meliá, Jose Alberto Revilla González (pp. 166-229
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