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Instituto de Parasitología y Biomedicina
"López - Neyra"
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[ Staff | Summary of Research | Funding Agencies | Publications | Doctoral Theses | Patents | Teaching]




NEUROIMMUNOLOGY OF INFLAMMATORY AND AUTOIMMUNE DISEASES



Group Leader
    • Mario Delgado Mora     
        email: mdelgado (@ipb.csic.es)
        Tlf: 958181665



    Staff Research Posdoctoral
    • Jenny Karina Campos Salinas     


    Staff Research Predoctoral
    • Ana Reyes Blázquez Caraballo     
    • Marina García Frutos     


    Technical Assistants
    • Marta Caro Moreno     
    • María Gemma Robledo Pérez     


    Authorized Staff
    • Marina Bermúdez Colmenero     

     

    SUMMARY OF RESEARCH


     

    NEUROIMMUNOLOGY OF INFLAMMATORY AND AUTOIMMUNE DISEASES

     

    Neuroimmunlogy is the field of the Biomedicine that studies the bidirectional communication that exists between the neuroendocrine and immune systems. This communication is mediated by several molecules (cytokines, neuropeptides and hormones) synthesized and secreted by cells of both systems in response to certain stimuli, and which through specific receptors expressed in such cells, regulate in an autocrine, paracrine and/or systemic way the function of both systems. Such regulation is critical for the maintenance of the body homeostasis. In fact, when a tissue damage or distress occurs, i.e. trauma, infection, inflammatory response or autoimmune disease, the organism responds secreting some of these mediators. Therefore, it has been suggested that several of these neuroimmune mediators participate in the mediation, prevention or repair of such damage.


     
     


    The interest of my research team is focused in the study of the production by immune cells (mainly lymphocytes and macrophages) of certain neupeptides/neurohormones that have been previously isolated in the neuroendocrine system, in the characterization of their receptors and mechanisms of actions in such cells, as well as the possible physiological role played by these mediators in different aspects of the immune and inflammatory response. In the last 12 years our work has been centered in the characterization of the vasoactive intestinal peptide (VIP) and related peptides of the family (i.e., PACAP) as neuroimmune mediators. VIP is a 28-aa peptide isolated firstly in the gastrointestinal tract by its vasodilatatory capacity, but that it was later described as an ubiquitous neuropeptide with a wide range of functions in almost all tissues. Our work has mainly consisted in the identification of VIP as a possible "cytokine" produced by T lymphocytes (mainly type 2) in response to antigenic and inflammatory stimuli, which acting through its binding to three specific receptors expressed in lymphocytes, macrophages and neutrophils, and acting through a complex network of intracellular transduction signals (including NF-kB, AP-1, IRF-1, STAT-1, CBP, MEKKs, TBP, CREB,...), plays a key role in the regulation of the immune and inflammatory response, mainly acting as a potent anti-inflammatory agent and shifting the immune response to a Th2 type one. These two functional characteristics perfectly explain the therapeutic effect of VIP in several experimental models of inflammatory and autoimmune diseases containing both components, an exacerbated inflammatory response and/or a preferential Th1 type immune response, as endotoxic shock, rheumatoid arthritis, Crohn's disease, Parkinson's disease and brain trauma. In our current lines of investigation, we investigate the therapeutic effect of VIP in other autoimmune diseases including multiple sclerosis, type 1 diabetes, Hashimoto's thyroiditis and autoimmune myocarditis, as well as the cellular and molecular mechanisms involved.




       


    Although our studies have been mainly focused in VIP, we are also planning to investigate the characterization of other neurohormonal mediators, including ghrelin, adrenomedullin and urocortin, in the immune system, their possible therapeutic application in the previously described diseases, and based in their structures, the design of drugs more effective and resistant, as well as the application of a possible gene therapy.





     


    FUNDING AGENCIES LAST 5 YEARS

    - PAPEL DE CORTISTATINA EN LA REGULACION DE LA PNEUMONIA BACTERIANA. PROYECTO, PN2021 - PROY I+D GENERACION CONOC. - PID, Ref: PID2021-127755OB-I00, (2022 - 2024).

    - Nueva estrategia terapéutica para el tratamiento de enfermedades inflamatorias y autoinmunes: células madre mesenquimales versión 2.0 (ASC v2.0). PROYECTO, J.A.- Retos de la sociedad andaluza 2020, Ref: P20_01255, (2021 - 2022).

    - Development of cellular assays to detect altered LRRK2 kinase activity in Parkinson¨s disease.. PROYECTO, INTRAMURAL, Ref: 202120E056, (2021 - 2023).

    - Estudio de la haploinsuficiencia de cortistatina como modelo experimental de monosomia 1p36. PROYECTO, , Ref: 201920E046, (2019 - 2020).

    - PAPEL INMUNOMODULADOR DE CORTISTATINA EFECTO EN FUNCION TIMICA E INMUNOSENESCENCIA. PROYECTO, PN2018 - Proyectos I+D+i «Retos Investigación», Ref: RTI2018-100700-B-I00, (2019 - 2021).

    - Puesta en marcha del servicio de secuenciación masiva en la Unidad de Genómica del IPBLN. PROYECTO, INTRAMURAL, Ref: 201620E052, (2016 - 2018).

    - Regulación epigenética de la respuesta inflamatoria. PROYECTO, PN2016 -RETOS COLABORACION - PRG. RETOS DE LA SOC., Ref: RTC-2016-4955-1, (2016 - 2018).

    - ESTUDIO DEL PAPEL DE CORTISTATINA EN FIBROSIS: POTENCIAL APLICACION TERAPEUTICA EN ENFERMEDADES CRONICAS ASOCIADAS A DAÑO TISULAR. PROYECTO, PN2015 - PROY I+D+I - PRG. RETOS DE LA SOCIEDAD, Ref: SAF2015-67787-R, (2016 - 2019).

     

     

    PUBLICATIONS LAST 5 YEARS

    -Paola Alejandra Romecín; Meritxell Vinyoles; Belén López-Millán; Rafael Diaz de la Guardia; Noemi M Atucha; Sergi Querol; Clara Bueno; Raquel Benitez; Elena Gonzalez-Rey; Mario Delgado; Pablo Menéndez, Robust In Vitro and In Vivo Immunosuppressive and Anti-inflammatory Properties of Inducible Caspase-9-mediated Apoptotic Mesenchymal Stromal/Stem Cell, Stem Cells Translational Medicine, 2022, Vol. 11: 88-96, ARTÍCULO, Id:892524

    -Raquel Benitez; Marta Caro; Eduardo Andres-Leon; Francisco O'Valle; Mario Delgado, Cortistatin regulates fibrosis and myofibroblast activation in experimental hepatotoxic¿and cholestatic¿induced liver injury, British Journal of Pharmacology, 2022, Vol. 179: 2275-2296, ARTÍCULO, Id:888782

    -Ana Isabel Sánchez-Castillo; M. Rosario Sepúlveda; José Luis Marín-Teva; Miguel A. Cuadros; David Martín-Oliva; Elena González-Rey; Mario Delgado; Veronika E. Neubrand, Switching Roles: Beneficial Effects of Adipose Tissue-Derived Mesenchymal Stem Cells on Microglia and Their Implication in Neurodegenerative Diseases, Biomolecules, 2022, Vol. 12: 2192-219, ARTÍCULO DE REVISIÓN, Id:870212

    -Barriga, M.; Benitez, R.; Ferraz-de-Paula, V.; Garcia-Frutos, M.; Caro, M.; Robledo, G.; O'Valle, F.; Campos-Salinas, J.; Delgado, M., Protective role of cortistatin in pulmonary inflammation and fibrosis, British Journal of Pharmacology, 2021, Vol. 178: 4368-4388, ARTÍCULO, Id:866715

    -Belmonte-Reche, E.; Peñalver, P.; Caro-Moreno, M.; Mateos-Martín, M.L.; Adán, N.; Delgado, M.; González-Rey, E.; Morales, J.C., Silyl resveratrol derivatives as potential therapeutic agents for neurodegenerative and neurological diseases, European Journal of Medicinal Chemistry, 2021, Vol. 223: 113655, ARTÍCULO, Id:852375

    -Falo, C.P.; Benitez, R.; Caro, M.; Morell, M.; Forte-Lago, I.; Hernandez-Cortes, P.; Sanchez-Gonzalez, C.; O¿valle, F.; Delgado, M.; Gonzalez-Rey, E., The neuropeptide cortistatin alleviates neuropathic pain in experimental models of peripheral nerve injury, Pharmaceutics, 2021, Vol. 13: 7-947, ARTÍCULO, Id:852220

    -Rol, Á.; Todorovski, T.; Martin-Malpartida, P.; Escolà, A.; Gonzalez-Rey, E.; Aragón, E.; Verdaguer, X.; Vallès-Miret, M.; Farrera-Sinfreu, J.; Puig, E.; Fernández-Carneado, J.; Ponsati, B.; Delgado, M.; Riera, A.; Macias, M.J., Structure-based design of a Cortistatin analogue with immunomodulatory activity in models of inflammatory bowel disease, Nature Communications, 2021, Vol. 12: 1-1869, ARTÍCULO, Id:846339

    -Zanetti, S.R.; Romecin, P.A.; Vinyoles, M.; Juan, M.; Fuster, J.L.; Cámos, M.; Querol, S.; Delgado, M.; Menendez, P., Bone marrow MSC from pediatric patients with B-ALL highly immunosuppress T-cell responses but do not compromise CD19-CAR T-cell activity, Journal for ImmunoTherapy of Cancer, 2020, Vol. 8: , ARTÍCULO, Id:813117

    -de la Guardia, R.D.; Lopez-Millan, B.; Roca-Ho, H.; Bueno, C.; Gutiérrez-Agüera, F.; Fuster, J.L.; Anguita, E.; Zanetti, S.R.; Vives, S.; Nomdedeu, J.; Sackstein, R.; Lavoie, J.; Gónzalez-Rey, E.; Delgado, M.; Rosu-Myles, M.; Menendez, P., Bone marrow mesenchymal stem/stromal cells from risk-stratified acute myeloid leukemia patients are anti-inflammatory in in vivo preclinical models of hematopoietic reconstitution and severe colitis, Haematologica, 2019, Vol. 104: e54-e58, CARTA AL EDITOR, Id:744444

    -Neubrand, V.E.; Forte-Lago, I.; Caro, M.; Delgado, M., The atypical RhoGTPase RhoE/Rnd3 is a key molecule to acquire a neuroprotective phenotype in microglia 06 Biological Sciences 0601 Biochemistry and Cell Biology, Journal of Neuroinflammation, 2018, Vol. 15: 1-343, ARTÍCULO, Id:739307

    -Benitez, R.; Delgado-Maroto, V.; Caro, M.; Forte-Lago, I.; Duran-Prado, M.; O¿Valle, F.; Lichtman, A.H.; Gonzalez-Rey, E.; Delgado, M., Vasoactive intestinal peptide ameliorates acute myocarditis and atherosclerosis by regulating inflammatory and autoimmune responses, Journal of Immunology, 2018, Vol. 200: 3697-3710, ARTÍCULO, Id:723202

    -Pablo Peñalver; Efres Belmonte-Reche; Norma Adán; Marta Caro; María Luisa Mateos-Martín; Mario Delgado; Elena González-Rey; Juan Carlos Morales, Alkylated resveratrol prodrugs and metabolites as potential therapeutics for neurodegenerative diseases, European Journal of Medicinal Chemistry, 2018, Vol. 146: 123-138, ARTÍCULO, Id:713336


     

     

    DOCTORAL THESES LAST 5 YEARS

     

    2022

    Raquel Benitez Gil

    "Análisis del papel del neuropéptido cortistatina en fibrosis hepática"

    Instituto de Parasitología y Biomedicina "López-Neyra" CSIC

     

     
    2021

    Margarita Barriga García-Mauriño

    Papel de Cortistatina en fibrosis crónica: potencial aplicación terapéutica en esclerodermia y fibrosis pulmonar idiopática

    IPBLN CSIC

     

     

     

     


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