Person:
Regueiro González-Barros, José Ramón

First Name

José Ramón

Last Name

Regueiro González-Barros

URI

https://hdl.handle.net/20.500.14352/79598

Affiliation

Universidad Complutense de Madrid

Faculty / Institute

Medicina

Department

Inmunología, Oftalmología y ORL

Area

Inmunología

Identifiers

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Search Results

Now showing 1 - 10 of 56

TCR signal strength controls thymic differentiation of discrete proinflammatory gamma-delta T cell subsets
(Nature immunology, 2016) Muñoz Ruiz, Miguel; Ribot, Julie C; Grosso, Ana R; Gonçalves Sousa, Natacha; Pamplona, Ana; Pennington, Daniel J; Regueiro González-Barros, José Ramón; Fernández Malavé, Edgar; Silva Santos, Bruno
The mouse thymus produces discrete gd T cell subsets that make either interferon-g (IFN-g) or interleukin 17 (IL-17), but the role of the T cell antigen receptor (TCR) in this developmental process remains controversial. Here we show that Cd3g+/− Cd3d+/− (CD3 double-haploinsufficient (CD3DH)) mice have reduced TCR expression and signaling strength on gd T cells. CD3DH mice had normal numbers and phenotypes of ab thymocyte subsets, but impaired differentiation of fetal Vg6+ (but not Vg4+) IL-17- producing gd T cells and a marked depletion of IFN-g-producing CD122+ NK1.1+ gd T cells throughout ontogeny. Adult CD3DH mice showed reduced peripheral IFN-g+ gd T cells and were resistant to experimental cerebral malaria. Thus, TCR signal strength within specific thymic developmental windows is a major determinant of the generation of proinflammatory gd T cell subsets and their impact on pathophysiology.
Human congenital T-cell receptor disorders
(LymphoSign Journal, 2015) Marín Marín, Ana Victoria; Garcillán Goyoaga, Beatriz de; Jiménez Reinoso, Anaïs; Muñoz Ruiz, Miguel; Briones Contreras, Alejandro; Fernández Malavé, Edgar; Recio Hoyas, María José; Regueiro González-Barros, José Ramón
Immunodeficiencies of most T-cell receptor (TCR) components (TCRID) have been reported in almost 40 patients worldwide who have also, at times, shown signs of autoimmunity. We updated their clinical, immunological, and molecular features with an emphasis on practical diagnosis, as the range of the disorder grows in complexity with new partial defects. Cellular and animal models are also reviewed and in some cases reveal their limitations for predicting TCRID immunopathology.
T-cell receptor complex deficiency
(Primary immunodeficiency diseases, a molecular and genetic approach, 2013) Regueiro González-Barros, José Ramón; Recio Hoyas, María José
The CD3 Conformational Change in the gd T Cell Receptor Is Not Triggered by Antigens but Can Be Enforced to Enhance Tumor Killing
(Cell Reports, 2014) Dopfer, Elaine P; Hartl, Frederike A; Oberg, Hans-Heinrich; Siegers, Grabrielle M; Yousefi, S. Sascha; Kock, Sylvia; Fiala, Gina J; Garcillán Goyoaga, Beatriz de; Sandstrom, Andrew; Alarcón, Balbino; Regueiro González-Barros, José Ramón; Kabelitz, Dieter; Adams, Erin J; Minguet, Susana; Wesch, Daniela; Fisch, Paul; Schamel, Wolfgang W.A.
Activation of the T cell receptor (TCR) by antigen is the key step in adaptive immunity. In the ab TCR antigen induces a conformational change at the CD3 subunits (CD3 CC) that is absolutely required for abTCR activation. Here, we demonstrate that the CD3 CC is not induced by antigen stimulation of the mouse G8 or the human Vg9Vd2 gdTCR. We find that there is a fundamental difference between the activation mechanisms of the abTCR and gdTCR that map to the constant regions of the TCRab/gd heterodimers. Enforced induction of CD3 CC with a less commonly used monoclonal anti-CD3 promoted proximal gdTCR signaling but inhibited cytokine secretion. Utilizing this knowledge, we could dramatically improve in vitro tumor cell lysis by activated human gd T cells. Thus, manipulation of the CD3 CC might be exploited to improve clinical gd T cellbased immunotherapies.
Primary T-cell immunodeficiency with functional revertant somatic mosaicism in CD247
(The Journal of Allergy and Clinical Inmunology, 2017) Marín Marín, Ana Victoria; Jiménez Reinoso, Anaïs; Briones Contreras, Alejandro; Muñoz Ruiz, Miguel; Aydogmus, Cigdem; Pasick, Luke J; Couso, Jorge; Mazariegos, Marina S; Álvarez Prado, Ángel F; Blázquez Moreno, Alfonso; Cipe, Funda E; Haskologlu, Sule; Dogu, Figen; Morín, Matías; Moreno Pelayo, Miguel A; García Sánchez, Félix; Gil Herrera, Juana; Fernández Malavé, Edgar; Reyburn, Hugh T; Ramiro, Almudena R; Ikinciogullari,, Aydan; Recio Hoyas, María José; Regueiro González-Barros, José Ramón; Garcillán Goyoaga, Beatriz de
Fat: Quality, or Quantity? What Matters Most for the Progression of Metabolic Associated Fatty Liver Disease (MAFLD)
(Biomedicines, 2021) Estévez-Vázquez, Olga; Benedé-Ubieto, Raquel; Guo, Feifei; Gómez-Santos, Beatriz; Aspichueta, Patricia; Reissing, Johanna; Bruns, Tony; Sanz-García, Carlos; Sydor, Svenja; Bechmann, Lars P; Maranillo Alcaide, Eva; Sañudo Tejero, José Ramón; Vázquez Osorio, María Teresa; Lamas-Paz, Arantza; Morán, Laura; Mazariegos, Marina S; Ciudin, Andreea; Pericàs, Juan M.; Peligros, María Isabel; Vaquero, Javier; Martínez-Naves, Eduardo; Liedtke, Christian; Regueiro González-Barros, José Ramón; Trautwein, Christian; Bañares Cañizares, Rafael; Cubero Palero, Francisco Javier; Nevzorova, Yulia A.
Objectives: Lately, many countries have restricted or even banned transfat, and palm oil has become a preferred replacement for food manufacturers. Whether palm oil is potentially an unhealthy food mainly due to its high content of saturated Palmitic Acid (PA) is a matter of debate. The aim of this study was to test whether qualitative aspects of diet such as levels of PA and the fat source are risk factors for Metabolic Syndrome (MS) and Metabolic Associated Fatty Liver Disease (MAFLD). Methods: C57BL/6 male mice were fed for 14 weeks with three types of Western diet (WD): 1. LP-WD—low concentration of PA (main fat source—corn and soybean oils); 2. HP-WD—high concentration of PA (main fat source—palm oil); 3. HP-Trans-WD—high concentration of PA (mainly transfat). Results: All types of WD caused weight gain, adipocyte enlargement, hepatomegaly, lipid metabolism alterations, and steatohepatitis. Feeding with HP diets led to more prominent obesity, hypercholesterolemia, stronger hepatic injury, and fibrosis. Only the feeding with HP-Trans-WD resulted in glucose intolerance and elevation of serum transaminases. Brief withdrawal of WDs reversed MS and signs of MAFLD. However, mild hepatic inflammation was still detectable in HP groups. Conclusions: HP and HP-Trans-WD play a crucial role in the genesis of MS and MAFLD.
Enrichment of the rare CD41 gd T-cell subset in patients with atypical CD3d deficiency
(Journal of Allergy and Clinical Immunology, 2014) Garcillán Goyoaga, Beatriz de; Mazariegos, Marina S; Fisch, Paul; Resh, Peter C.; Muñoz Ruiz, Miguel; Gil Herrera, Juana; López Granados, Eduardo; Fernández Malavé, Edgar; Regueiro González-Barros, José Ramón
A leaky mutation in CD3D differentially affects αβ and γδ T cells and leads to a Tαβ−Tγδ+B+NK+ human SCID
(The Journal of Clinical Investigation, 2011) Gil Calle, Juana Nelly; Busto, Elena M; Garcillán Goyoaga, Beatriz de; Chean, Carmen; García Rodríguez, María Cruz; Díaz Alderete, Andrea; Navarro, Joaquín; Reiné Gutiérrez, Jesús; Mencía, Ángeles; Gurbindo, Dolores; Beléndez, Cristina; Gordillo, Isabel; Duchniewicz, Marlena; Höhne, Kerstin; García Sánchez, Félix; Fernández Cruz, Eduardo; López Granados, Eduardo; Schamel, Wolfgang W.A.; Moreno Pelayo, Miguel A; Recio Hoyas, María José; Regueiro González-Barros, José Ramón
T cells recognize antigens via their cell surface TCR and are classified as either αβ or γδ depending on the variable chains in their TCR, α and β or γ and δ, respectively. Both αβ and γδ TCRs also contain several invariant chains, including CD3δ, which support surface TCR expression and transduce the TCR signal. Mutations in variable chains would be expected to affect a single T cell lineage, while mutations in the invariant chains would affect all T cells. Consistent with this, all CD3δ-deficient patients described to date showed a complete block in T cell development. However, CD3δ-KO mice have an αβ T cell–specific defect. Here, we report 2 unrelated cases of SCID with a selective block in αβ but not in γδ T cell development, associated with a new splicing mutation in the CD3D gene. The patients’ T cells showed reduced CD3D transcripts, CD3δ proteins, surface TCR, and early TCR signaling. Their lymph nodes showed severe T cell depletion, recent thymus emigrants in peripheral blood were strongly decreased, and the scant αβ T cells were oligoclonal. T cell–dependent B cell functions were also impaired, despite the presence of normal B cell numbers. Strikingly, despite the specific loss of αβ T cells, surface TCR expression was more reduced in γδ than in αβ T cells. Analysis of individuals with this CD3D mutation thus demonstrates the contrasting CD3δ requirements for αβ versus γδ T cell development and TCR expression in humans and highlights the diagnostic and clinical relevance of studying both TCR isotypes when a T cell defect is suspected.
Abnormal liver function test in patients infected with Coronavirus (SARS-CoV-2): a retrospective Single-Center Study from Spain
(Journal of Clinical Medicine, 2021) Benedé Ubieto, Raquel; Estevez Vázquez, Olga; Flores-Perojo, Vicente; Macías-Rodríguez, Ricardo U.; Ruiz-Margáin, Astrid; Martinez Naves, Eduardo; Regueiro González-Barros, José Ramón; Avila, Matías A.; Trautwein, Christian; Bañares, Rafael; Bosch, J.; Cubero Palero, Francisco Javier; Nevzorova, Yulia A.
The outbreak of the novel coronavirus SARS-CoV-2 epidemic has rapidly spread and still poses a serious threat to healthcare systems worldwide. In the present study, electronic medical records containing clinical indicators related to liver injury in 799 COVID-19-confirmed patients admitted to a hospital in Madrid (Spain) were extracted and analyzed. Correlation between liver injury and disease outcome was also evaluated. Serum levels of Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma-glutamyltransferase (GGT), Alkaline phosphatase (ALP), Lactate dehydrogenase (LDH) and AST/ALT ratio were elevated above the Upper Limit of Normal (ULN) in 25.73%, 49.17%, 34.62%, 24.21%, 55.84% and 75% of patients, respectively. Interestingly, significant positive correlation between LDH levels and the AST/ALT ratio with disease outcome was found. Our data showed that SARS-CoV-2 virus infection leads to mild, but significant changes in serum markers of liver injury. The upregulated LDH levels as well as AST/ALT ratios upon admission may be used as additional diagnostic characteristic for COVID-19 patients.
Natural killer cell hyporesponsiveness and impaired development in a CD247-deficient patient
(Journal of Allergy and Clinical Immunology, 2016) Valés Gómez, Mar; Esteso, Gloria; Aydogmus, Cigdem; Blázquez Moreno, Alfonso; Marín Marín, Ana Victoria; Briones Contreras, Alejandro; Garcillán Goyoaga, Beatriz de; García Cuesta, Eva; López Cobo, Sheila; Haskologlu, Sule; Moraru, Manuela; Cipe, Funda E; Dobbs, Kerry; Dogu, Figen; Parolini, Silvia; Notarangelo, Luigi D.; Vilches, Carlos; Recio, María J.; Regueiro González-Barros, José Ramón; Ikinciogullari, Aydan; Reyburn, Hugh T. R