José I. Rodríguez Barbosa
Name of the laboratory
- Laboratory of Transplantation Immunobiology
- Edificio Nuevos Institutos de Investigación
- Campus de Vegazana s/n
- 24071 León, Spain
- 34 987 293 079
Members of the laboratory
- Unit Coordinator. Professor of Immunology
José I. Rodríguez Barbosa firstname.lastname@example.org
- Miguel Servet Investigator. Associate Professor of Immunology
Maria Luisa del Río González email@example.com
Alexia Martín Vega
Irene Carnicero Frutos
María Martin García
- Undergraduate students of Biotechnology and Biological Sciences
Rebeca Gutiérrez Cozar
Adrián Núñez Soto
- PhD students
Irene de Vigo
Rejection of allogeneic tissues and organs is an immunological phenomenon mediated by T cells and antibodies. The rejection of transplanted vascularized solid organs across MHC histocompatibility barriers requires continuous and prolonged use of immunosuppressive drugs, which are responsible for long-term serious side effects. Therefore, those therapeutic interventions or strategies to reduce or ideally eliminate immunosuppressive medication that allow the induction of immunological tolerance would achieve long-term graft survival and the improvement in the quality of life of transplanted patients.
The final goal of our laboratory is the identification and validation of molecular targets essential for the exchange of information between dendritic cells / T cells and T/ B cells for the modulation of the allogeneic humoral and cellular mediated immune responses.
1) Prevention of allograft rejection by interfering with the collaboration of dendritic cells / B / T cells through blockade of costimulatory signals or the enhancement of negative signaling to T cells (coinhibitory signals).
2) Prevention of rejection by the selective elimination of T cells responsive to alloantigen, targeting molecules that are restrictively expressed upon T cell activation.
To address these objectives, we applied biochemical techniques, molecular biology, cellular and animal models of skin and bone marrow transplantation. We amplify genes of interest involved in particular pathways of cell interaction, which are then cloned and expressed as membrane bound proteins and soluble proteins (extracellular regions). Soluble recombinant proteins are purified from culture supernatant of transfected cells and use as antigens for the generation of antibodies with different effector functions (agonist, antagonist, depleting, non-depleting). Finally, these antibodies and recombinant proteins are used as therapeutic tools in vitro and in vivo to test their efficacy in preventing allogeneic immune responses across different histocompatibility barriers to dissect the mechanisms involved in graft rejection and tolerance.
The ultimate goal of the lab is to prove that the experimental strategies developed in the course of our studies are able to prevent rejection in in vivo animal models of skin and bone marrow transplantation across different MHC histocompatibility barriers , where the rejection response is mediated by CD4 and CD8 T lymphocytes and anti-donor specific antibodies.
- Divya Sekar, Luisa Govene, María Luisa del Río, Evelyn Sirait-Fischer, Annika Fink, Bernhard Brüne, Jose Ignacio Rodriguez-Barbosa, Andreas Weigert. Downregulation of BTLA activates NKT cells and promotes tumor immune control in a mouse model of mammary carcinoma. International Journal of Molecular Sciences (Manuscript ID: ijms-275430, accepted). 2018.
- Modulation of cytotoxic responses by targeting CD160 prolongs skin graft survival across major histocompatibility class I barrier. Del Rio ML, Bravo Moral AM, Fernandez-Renedo C, Buhler L, Perez-Simon JA, Chaloin O, Alvarez Nogal R, Fernandez-Caso M, Rodriguez-Barbosa JI. Transl Res. 2017 Mar;181:83-95.e3. doi: 10.1016/j.trsl.2016.09.004. Epub 2016 Sep 15. PMID: 27702550
- T follicular helper expansion and humoral-mediated rejection are independent of the HVEM/BTLA pathway. Rodriguez-Barbosa JI, Fernandez-Renedo C, Moral AMB, Bühler L, Del Rio ML. Cell Mol Immunol. 2017 Jun;14(6):497-510. doi: 10.1038/cmi.2015.101. Epub 2016 Feb 29. PMID: 26924526. Free PMC Article
- G. Roncador, G., P. Engel, L. Maestre, A. P. Anderson, J. L. Cordell, M. S. Cragg, V. C. Serbec, M. Jones, V. J. Lisnic, L. Kremer, D. Li, F. Koch-Nolte, N. Pascual, J. I. Rodriguez-Barbosa, R. Torensma, H. Turley, K. Pulford, and A. H. Banham. 2016. The European antibody network's practical guide to finding and validating suitable antibodies for research. mAbs 8(1): 27-36.
- M.L. del Rio, C. Fernandez-Renedo, O. Chaloin, S. Scheu, K. Pfeffer, Y. Shintani, J. A. Perez-Simon, P. Schneider, and J.I. Rodriguez-Barbosa. 2016. Immunotherapeutic targeting of LIGHT/LTbetaR/HVEM pathway fully recapitulates the reduced cytotoxic phenotype of LIGHT-deficient T cells. mAbs 11: 1-13.
- H. Arefanian, E. B. Tredget, D. C. Mok, Q. Ramji, S. Rafati, J.I. Rodriguez-Barbosa, G. S. Korbutt, R. V. Rajotte, R. G. Gill, and G. R. Rayat. 2016. Porcine Islet-Specific Tolerance Induced by the Combination of Anti-LFA-1 and Anti-CD154 mAbs Is Dependent on PD-1. Cell transplantation 25: 327-342.
- Sanchez-Abarca, L. I., E. Hernandez-Galilea, R. Lorenzo, C. Herrero, A. Velasco, S. Carrancio, T. Caballero-Velazquez, J.I. Rodriguez-Barbosa, M. Parrilla, C. Del Canizo, J. San Miguel, J. Aijon, and J. A. Perez-Simon. 2015. Human Bone Marrow Stromal Cells Differentiate Into Corneal Tissue and Prevent Ocular Graft-Versus-Host Disease in Mice. Cell transplantation 24: 2423-2433.
- M.L. del Rio, C. Fernandez-Renedo, S. Scheu, K. Pfeffer, Y. Shintani, M. Kronenberg, O. Chaloin, P. Schneider, and J.I. Rodriguez-Barbosa. 2014. Therapeutic blockade of LIGHT interaction with herpesvirus entry mediator and lymphotoxin beta receptor attenuates in vivo cytotoxic allogeneic responses. Transplantation 98: 1165-1174.
- S.J. Allen,, A. Rhode-Kurnow, K. R. Mott, X. Jiang, D. Carpenter, J.I. Rodriguez-Barbosa, C. Jones, S. L. Wechsler, C. F. Ware, and H. Ghiasi. 2014. Interactions between herpesvirus entry mediator (TNFRSF14) and latency-associated transcript during herpes simplex virus 1 latency. Journal of virology 88: 1961-1971.
- Maria-Luisa del Rio, Jörg D. Seebach, and Jose-Ignacio Rodriguez-Barbosa. Negative signaling pathways for the control of xenogeneic immune responses. Xenotransplantation. 2013 Nov-Dec;20 (6) :397-406. 2013.
- Maria-Luisa del Rio, Pascal Schneider, Carlos Fernández-Renedo, Jose Antonio Pérez Simón, and Jose-Ignacio Rodriguez-Barbosa. LIGHT/HVEM/LTbR interaction as a target for the modulation of the allogeneic immune response in transplantation. American Journal of Transplantation. 13 (3) :541-51, 2013.
- CroatiaStipan JonjicUniversity of Rijeka
- DenmarkJakub Z. KaczmarekSanovo Biotech A/S
- FranceAndré PèlegrinInstitut de Recherche en Cancérologie de Montpellier, IRCM
- FranceArmand BensussanHôpital Saint Louis
- FrancePierre LafayeInstitut Pasteur
- GermanyFriedrich Koch-NolteUniversity Medical Center Hamburg-Eppendorf
- HungaryJohanna SymmonsEnglish & Scientific Consulting Kft. (SCICONS)
- HungaryPeter BaloghClinical Center, University of Pecs
- ItalyFabio MalavasiUniversity of Torino Medical School
- RussiaAlexander FilatovInstitute of Immunology
- RussiaAlexander TaraninInstitute of Molecular and Cellular Biology
- SloveniaVladka Čurin ŠerbecBlood Trasfusion Centre of Slovenia
- SpainGiovanna RoncadorCentro Nacional de Investigaciones Oncológicas
- SpainJosé I. Rodríguez BarbosaEdificio Nuevos Institutos de Investigación
- SpainLeonor KremerCentro Nacional de Biotecnología/CSIC
- SpainNúria PascualInstitute for Advanced Chemistry of Catalonia (IQAC-CSIC)
- SpainPablo EngelFaculty of Medicine and Medical Sciences, University of Barcelona
- United KingdomUniversity of OxfordLRF Haemato-oncology Group
- United KingdomVertebrate Antibodies Limited (VAL)
- United KingdomKing's College LondonSt. John's Institute of Dermatology