Inicio de sesión

​​Contact​​

Dr. Ramón Merino

Phone: (+34) 942 206855 / Fax: (+34) 942 2656399

Email: merinor@unican.es​

Mailing address: IBBTEC. C/ Albert Einstein 22, PCTCAN, 39011 Santander​

Chronic inflammatory and autoimmune diseases

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Principal Investigator

Dr. Ramón Merino Pérez, Staff Scientist (CSIC)​​

  

Other personnel

  • Esther Tamayo Revuelta, Postdoctoral
  • Marta Alonso Varela, Predoctoral
  • Iván Gómez Herrero, Laboratory Technician


Research lines

Upon antigenic encounter naïve CD4+ T cells differentiate into distinct functional Th subpopulations with defined patterns of cytokine production and effector functions. Due to their antagonism in the control of lymphoid homeostasis, our interest has been focused in the study of regulatory CD4+CD25+ T cells (Tregs; tolelance) and Th17 cells (involved in the pathogenesis of different autoimmune/inflammatory diseases). Strikingly, both subpopulations are induced after antigenic stimulation in the presence of a common cytokine; TGF-ß. Recent studies show that TGF-ß promotes the generation of Th17 cells together with pro-inflammatory cytokines such as IL-6. In view of the dual role of TGF-ß in the differentiation of Tregs and Th17 and in the antagonistic activity of both populations in the control of immune tolerance, our research is focused in the study of the molecular mechanisms that modulate TGF-ß activity on naïve CD4+ T lymphocytes and that determine the differentiation, functional activity and stability of Tregs and Th17 subpopulations. Those studies are performed using mutant mice that overexpress or are deficient in particular regulators of TGF-ß signalling, in vitro models of Tregs and Th17 differentiation and function and in vivo models of Th17-dependent autoimmune diseases in mice.
In addition, our group is interested in the study of the cause-effect relationship among the development of rheumatoid arthritis and atherosclerosis in experimental animal models of autoimmune arthritis. We are particularly interested in the study of the immunomodulatory properties of ApoE after its overexpression in vivo with lentiviral vectors.

 

Funding

Mecanismos moduladores de la diferenciación y actividad funcional de los linfocitos T CD4+CD25+ reguladores. Ministerio de Ciencia e Innovación (SAF2011-22463). 2012-2014.
Desarrollo de nuevos procedimientos diagnósticos y terapéuticos basados en la tecnología de GPBP. MICINN-INNPACTO (IPT-2011-1527-010000). Entidades participantes: Fibrostatin S.L. (Valencia), Universidad de Valencia, Universidad de Cantabria (UC). Sept-2011-Dec-2014.


Relevant publications (last 10 years)

  • Context-dependent regulation of Th17-associated genes and IFNγ expression by the transcription factor NFAT5. Alberdi M, Iglesias M, Tejedor S, Merino R, López-Rodríguez C, Aramburu J.

    Immunol Cell Biol. 2016 Aug 1. doi: 10.1038/icb.2016.69. [PubMed]

  • Transgenic expression of soluble human CD5 enhances experimentally-induced autoimmune and anti-tumoral immune responses. Fenutría R, Martinez VG, Simões I, Postigo J, Gil V, Martínez-Florensa M, Sintes J, Naves R, Cashman KS, Alberola-Ila J, Ramos-Casals M, Soldevila G, Raman C, Merino J, Merino R, Engel P, Lozano F.
    PLoS One
    . 2014 Jan 15;9(1):e84895. doi: 10.1371/journal.pone.0084895. [PubMed]

  • Mice deficient in CD38 develop an attenuated form of collagen type II-induced arthritis. Postigo J, Iglesias M, Cerezo-Wallis D, Rosal-Vela A, García-Rodríguez S, Zubiaur M, Sancho J, Merino R, Merino J.
    PLoS One
    . 2012;7(3):e33534. doi: 10.1371/journal.pone.0033534. [PubMed]

  • Contribution of animal models to the study and treatment of systemic autoimmune disease. Merino J, Merino R.
    Reumatol Clin
    . 2008 Mar;4 Suppl 1:5-10. doi: 10.1016/S1699-258X(08)76132-1. [PubMed]

  • p27kip1 inhibits systemic autoimmunity through the control of regulatory T cell activity and differentiationM. Iglesias, J. Postigo, I. Santiuste, J. González, L. Buelta, E. Tamayo, J. Merino and R. Merino.
    Arthritis Rheum. 2013, 65: 343-354. DOI: 10.1002/art.37778. [PubMed]
  • J. Postigo, M. Iglesias, A. Rosal-Vela, S. García-Rodríguez, M. Zubiaur, J. Sancho, R. Merino* and J. Merino*. Mice deficient in CD38 develop an attenuated form of collagen type II-induced arthritis. PLoS ONE 2012, 7: e33534. DOI:10.1371/journal.pone.0033534. [pubmed]
  • J. Postigo., F. Genre, M. Iglesias, M. Fernández-Rey, L. Buelta, J.C. Rodríguez-Rey, J. Merino and R. Merino. Exacerbation of collagen type II-induced arthritis in ApoE deficient mice in association with the expansion of Th1 and Th17 cells. Arthritis Rheum. 2011, 63: 971-980. DOI: 10.1002/art.30220. [pubmed]
  • I. Santiuste, L. Buelta, M. Iglesias, F. Genre, F. Mazorra, S. Izui, J. Merino and R. Merino. B-cell overexpression of Bcl-2 cooperates with p21 deficiency for the induction of autoimmunity and lymphomas. J. Autoimmun. 2010, 35: 316-324. [pubmed]
  • M. Tramullas, A. Lantero, A. Díaz, N. Morchón, D. Merino, A. Villar, D. Buscher, R. Merino, J.M. Hurlé, J.C. Izpisúa-Belmonte, M.A. Hurlé. BMP and Activin membrane-bound inhibitor (BAMBI) reveals the involvement of the TGF-β family in pain modulation. J. Neurosci. 2010, 30: 1502-1511. [pubmed]
  • E. Tamayo, J. Postigo, J. González, M. Fernández-Rey, M. Iglesias, I. Santiuste, C. Riccardi, R. Rappuoli, G. del Giudice, R. Merino* and J. Merino*. The Glucocorticoid-Induced TNFR-Related protein (GITR) contributes to the systemic adjuvanticity of the Escherichia coli heat-labile enterotoxin. Eur. J. Immunol. 2010, 40: 754-763.
  • MªA. Ramos-Barrón, C. Gómez-Alamillo, I. Santiuste, C. Agüeros, L. San Cosme, A. Benito, T. Gimenez, J. Merino, R Merino and M Arias. Leflunomide derivative FK778 inhibits production of antibodies in an experimental nodel of alloreactive T-B cell interaction. Exp. Clin. Trasplant. 2009, 4: 218-224.
  • A.V. Villar, M. Llano, M. Cobo, V. Expósito, R. Merino, R. Martín-Durán, M.A. Hurlé, and J.F. Nistal. Gender differences of echocardiographic and gene expression patterns in human pressure overload left ventricular hypertrophy. J. Mol. Cell. Card. 2009, 46: 526-535.
  • E. Tamayo, J. Postigo, G. del Giudice, R. Rappuoli, A. Benito, H. Yagita, R. Merino* and J. Merino*. Involvement of the intrinsic and extrinsic cell death pathways in the induction of apoptosis of mature lymphocytes by the Escherichia coli heat-labile enterotoxin. Eur. J. Immunol. 2009, 39: 439-446.
  • F. Revert, R. Merino, C. Monteagudo, J. Macias, A. Peydró, J. Alcácer, P. Muniesa, R. Marquina, M. Blanco, M. Iglesias, F. Revert-Ros, J. Merino and J. Saus. Increased GPBP expression induces type IV collagen disorganization and deposit of IgA in glomemular basement membrane. Am. J. Pathol. 2007, 171:1419-1430.
  • J. González, E. Tamayo, I. Santiuste, R. Marquina, L. Buelta, M.A. González-Gay, S. Izui, M. López-Hoyos, J. Merino and R. Merino. CD4+CD25+ T cell-dependent inhibition of autoimmunity in transgenic mice overexpressing human Bcl-2 in T lymphocytes. J. Immunol. 2007, 178: 2778–2786.
  • D. San Segundo, J.C. Ruiz, G. Fernández-Fresnedo, M. Izquierdo, C. Gómez-Alamillo, R. Merino, M.J. Benito, E. Cacho, E. Rodrigo, R. Palomar, M. López-Hoyos, M. Arias. Calcineurin inhibitors, but not rapamycin, reduce percentages of CD4+CD25+FOXP3+ regulatory T cells in renal transplant recipients. Transplantation 2006, 82:550-557.
  • E. Tamayo, R. Merino, J. González-Rojas, R. Marquina, I. Santiuste, J.A. Amado, R. Rappuoli, G. Del Giudice and J. Merino. The Escherichia coli heat-labile enterotoxin induces apoptosis of immature lymphocytes in vivo via a glucocorticoid-dependent pathway. Eur. J. Immunol. 2005, 35:3505-3515.
  • P. Mora, I. Masip, N. Cortés, R. Marquina, R. Merino, J. Merino, T. Carbonell, I. Mingarro, A. Messeguer and E. Pérez-Payá. Identification from a positional scanning peptoid library of in vivo active compounds that neutralize bacterial endotoxins. J. Med. Chem. 2005, 48:1265-1268.
  • V. Zuzarte-Luis, J.A. Montero-Simon, J. Rodríguez-León, R. Merino, J.C. Rodriguez-Rey and J.M. Hurle. A new role for BMP5 during limb development acting through the synergic activation of Smad and MAPK pathways. Dev. Biol. 2004, 272:39-52.
  • Vossenaar ER, MAM van Boekel, WJ van Venrooij, M López-Hoyos, J Merino, R Merino and LAB Joosten. Absence of citrulline-specific antibodies in animal models of arthritis. Arthritis Rheum. 2004, 50:2370-2372.
  • R. Marquina, M.A. Díez, M. López-Hoyos, L. Buelta, A. Kuroki, S. Kikuchi, J. Villegas, M. Pihlgren, C.A. Siegrist, M. Arias, S. Izui, J. Merino and R. Merino. Inhibition of B cell death causes the development of an IgA nephropathy in (NZW x C57BL/6)F1-bcl-2 transgenic mice. J. Immunol. 2004, 172:7177-7185.
  • A. Kuroki, T. Moll, M. López-Hoyos, L. Fossati-Jimack, N. Ibnou-Zekri, S. Kikuchi, J. Merino, R. Merino and S. Izui. Enforced BCL-2 expression in B lymphocytes induces rheumatoid factor and anti-DNA production, but the Yaa mutation promotes only anti-DNA production. Eur. J. Immunol. 2004, 34:1077-1084.
  • R. Merino and J.M. Hurlé. The molecular basis of retinoid action in tumours. Trends Mol. Med. 2003, 9:509-511.
  • M. López-Hoyos, R. Marquina, E. Tamayo, J. González-Rojas, S. Izui, R. Merino* and J. Merino*. Defects in the regulation of B cell apoptosis are required for the production of citrullinated peptide autoantibodies in mice. Arthritis Rheum. 2003, 48:2353-2361.
  • J. Chimal-Monroy, J. Rodriguez-Leon, J.A. Montero, Y. Gañan, D. Macias, R. Merino and J.M. Hurle. Analysis of the molecular cascade responsible for mesodermal limb chondrogenesis: Sox genes and BMP signaling. Dev. Biol. 2003, 257:292-301.