Person: Muñoz Ruiz, Miguel
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First Name
Miguel
Last Name
Muñoz Ruiz
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Inmunología, Oftalmología y ORL
Area
Identifiers
7 results
Search Results
Now showing 1 - 7 of 7
Item 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 RamónImmunodeficiencies 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.Item 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 deItem 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 RamónItem Human CD3γ, but not CD3δ, haploinsufficiency differentially impairs γδ versus αβ surface TCR expression(BMC Immunology, 2013) Muñoz Ruiz, Miguel; Pérez Flores, Verónica; Garcillán Goyoaga, Beatriz de; Guardo, Alberto C; Mazariegos, Marina S; Takada, Hidetoshi; Allende Martínez, Luis Miguel; Kilic, Sara S; Sanal, Ozden; Roifman, Chaim M; López Granados, Eduardo; Recio Hoyas, María José; Martínez Naves, Eduardo; Fernández Malavé, Edgar; Regueiro González-Barros, José RamónBackground: The T cell antigen receptors (TCR) of αβ and γδ T lymphocytes are believed to assemble in a similar fashion in humans. Firstly, αβ or γδ TCR chains incorporatea CD3δε dimer, then a CD3γε dimer and finally a ζζ homodimer, resulting in TCR complexes with the same CD3 dimer stoichiometry. Partial reduction in the expression of the highly homologous CD3γ and CD3δ proteins would thus be expected to have a similar impact in the assembly and surface expression of both TCR isotypes. To test this hypothesis, we compared the surface TCR expression of primary αβ and γδ T cells from healthy donors carrying a single null or leaky mutation in CD3G (γ+/−) or CD3D (δ+/−, δ+/leaky) with that of normal controls. Results: Although the partial reduction in the intracellular availability of CD3γ or CD3δ proteins was comparable as a consequence of the mutations, surface TCR expression measured with anti-CD3ε antibodies was significantly more decreased in γδ than in αβ T lymphocytes in CD3γ+/− individuals, whereas CD3δ+/− and CD3δ+/leaky donors showed a similar decrease of surface TCR in both T cell lineages. Therefore, surface γδ TCR expression was more dependent on available CD3γ than surface αβ TCR expression. Conclusions: The results support the existence of differential structural constraints in the two human TCR isotypes regarding the incorporation of CD3γε and CD3δε dimers, as revealed by their discordant surface expression behaviour when confronted with reduced amounts of CD3γ, but not of the homologous CD3δ chain. A modified version of the prevailing TCR assembly model is proposed to accommodate these new data.Item CD3G or CD3D Knockdown in Mature, but Not Immature, T Lymphocytes Similarly Cripples the Human TCRαβ Complex(Frontiers in Cell and Developmental Biology, 2021) Garcillán Goyoaga, Beatriz de; Fuentes, Patricia; Marín Marín, Ana Victoria; Fernández Megido, Rebeca; Chacón Arguedas, Carlos Daniel; S. Mazariegos, Marina; González Laborda, Raquel; Jiménez Reinoso, Anaïs; Muñoz Ruiz, Miguel; Cárdenas Mastracusa, Paula; Fernández-Malavé, Edgar; Toribio, Maria Luisa; Regueiro González-Barros, José RamónThe human αβ T-cell receptor (TCR) is composed of a variable heterodimer (TCRαβ) and three invariant dimers (CD3γε, CD3δε, and ζζ/CD2472). The role of each invariant chain in the stepwise interactions among TCR chains along the assembly is still not fully understood. Despite the high sequence homology between CD3γ and CD3δ, the clinical consequences of the corresponding immunodeficiencies (ID) in humans are very different (mild and severe, respectively), and mouse models do not recapitulate findings in human ID. To try to understand such disparities, we stably knocked down (KD) CD3D or CD3G expression in the human Jurkat T-cell line and analyzed comparatively their impact on TCRαβ assembly, transport, and surface expression. The results indicated that TCR ensembles were less stable and CD3ε levels were lower when CD3γ, rather than CD3δ, was scarce. However, both defective TCR ensembles were strongly retained in the ER, lacked ζζ/CD2472, and barely reached the T-cell surface (<11% of normal controls) in any of the CD3 KD cells. This is in sharp contrast to human CD3γ ID, whose mature T cells express higher levels of surface TCR (>30% vs. normal controls). CD3 KD of human T-cell progenitors followed by mouse fetal thymus organ cultures showed high plasticity in emerging immature polyclonal T lymphocytes that allowed for the expression of significant TCR levels which may then signal for survival in CD3γ, but not in CD3δ deficiency, and explain the immunological and clinical disparities of such ID cases.Item gd T lymphocytes in the diagnosis of human T cell receptor immunodeficiencies(Frontiers in immunology, 2015) Garcillán Goyoaga, Beatriz de; Marín Marín, Ana Victoria; Jiménez Reinoso, Anaïs; Briones Contreras, Alejandro; Muñoz Ruiz, Miguel; García León, María J; Gil Calle, Juana Nelly; Allende Martínez, Luis Miguel; Martínez Naves, Eduardo; Toribio, Maria Luisa; Regueiro González-Barros, José RamónHuman T cell receptor (TCR) immunodeficiencies (TCRID) are rare autosomal recessive disorders caused by mutations affecting TCR, CD3, or CD247 chains, which share developmental, functional, and TCR expression defects (1). Their rapid diagnosis is fundamental for patient survival and early hematopoietic stemcell transplantation.Here,we propose that studying gd T cells, which are often neglected, can be helpful for a timely diagnosis. We thus offer a diagnostic flowchart and some lab tricks based on published cases.Item Inmunodeficiencias congénitas del receptor de antígeno de los linfocitos T(Inmunología, 2013) Mazariegos, Marina S; Muñoz Ruiz, Miguel; Reiné Gutiérrez, Jesús; Garcillán Goyoaga, Beatriz de; Recio Hoyas, María José; Fernández Malavé, Edgar; Regueiro González-Barros, José RamónLas inmunodeficiencias humanas del TCR son enfermedades autosómicas recesivas con baja prevalencia, caracterizadas por un defecto de expresión del TCR asociado a una linfopenia T selectiva (más leve en el caso de CD3γ, TCRα o CD247, o grave en el caso de CD3δ o CD3??). La ausencia congénita de componentes del TCR tiene un impacto diferencial en el desarrollo y función de los linfocitos T, que depende de la cadena del TCR afectada y de la especie, siendo en algunos casos diferente en los pacientes humanos en comparación con los modelos en ratones. El estudio del inmunofenotipo mediante citometría de flujo, junto con los estudios moleculares, proporciona información esencial para el diagnóstico y el tratamiento, que continúa siendo a día de hoy el trasplante de progenitores hematopoyéticos en los casos asociados a inmunodeficiencia grave.