Person:
Muñoz Ruiz, Miguel

Profile Picture
First Name
Miguel
Last Name
Muñoz Ruiz
URI
https://hdl.handle.net/20.500.14352/87166
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Medicina
Department
Inmunología, Oftalmología y ORL
Area
Identifiers
UCM identifierORCIDScopus Author IDDialnet ID

Filters

2013 - 20176
Reset filters

Settings

Author: Fernández Malavé, Edgar ×

Search Results

Now showing 1 - 6 of 6
  • Thumbnail Image
    Item
    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.
  • Thumbnail Image
    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 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.
  • Thumbnail Image
    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 de
  • Thumbnail Image
    Item
    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
  • Thumbnail Image
    Item
    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 Ramón
    Background: 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.
  • Thumbnail Image
    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 Ramón
    Las 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.