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T-cell-intrinsic Tif1α/Trim24 regulates IL-1R expression on TH2 cells and TH2 cell-mediated airway allergy.
Perez-Lloret, Jimena; Okoye, Isobel S; Guidi, Riccardo; Kannan, Yashaswini; Coomes, Stephanie M; Czieso, Stephanie; Mengus, Gabrielle; Davidson, Irwin; Wilson, Mark S.
Afiliación
  • Perez-Lloret J; Allergy and Anti-Helminth Immunity Laboratory, The Francis Crick Institute, Mill Hill Laboratories, London NW7 1AA, United Kingdom;
  • Okoye IS; Allergy and Anti-Helminth Immunity Laboratory, The Francis Crick Institute, Mill Hill Laboratories, London NW7 1AA, United Kingdom;
  • Guidi R; Allergy and Anti-Helminth Immunity Laboratory, The Francis Crick Institute, Mill Hill Laboratories, London NW7 1AA, United Kingdom;
  • Kannan Y; Allergy and Anti-Helminth Immunity Laboratory, The Francis Crick Institute, Mill Hill Laboratories, London NW7 1AA, United Kingdom;
  • Coomes SM; Allergy and Anti-Helminth Immunity Laboratory, The Francis Crick Institute, Mill Hill Laboratories, London NW7 1AA, United Kingdom;
  • Czieso S; Allergy and Anti-Helminth Immunity Laboratory, The Francis Crick Institute, Mill Hill Laboratories, London NW7 1AA, United Kingdom;
  • Mengus G; Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67400 Illkirch, France.
  • Davidson I; Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67400 Illkirch, France.
  • Wilson MS; Allergy and Anti-Helminth Immunity Laboratory, The Francis Crick Institute, Mill Hill Laboratories, London NW7 1AA, United Kingdom; mark.wilson@crick.ac.uk.
Proc Natl Acad Sci U S A ; 113(5): E568-76, 2016 Feb 02.
Article en En | MEDLINE | ID: mdl-26787865
There is a paucity of new therapeutic targets to control allergic reactions and forestall the rising trend of allergic diseases. Although a variety of immune cells contribute to allergy, cytokine-secreting αß(+)CD4(+) T-helper 2 (TH2) cells orchestrate the type-2-driven immune response in a large proportion of atopic asthmatics. To identify previously unidentified putative targets in pathogenic TH2 cells, we performed in silico analyses of recently published transcriptional data from a wide variety of pathogenic TH cells [Okoye IS, et al. (2014) Proc Natl Acad Sci USA 111(30):E3081-E3090] and identified that transcription intermediary factor 1 regulator-alpha (Tif1α)/tripartite motif-containing 24 (Trim24) was predicted to be active in house dust mite (HDM)- and helminth-elicited Il4(gfp+)αß(+)CD4(+) TH2 cells but not in TH1, TH17, or Treg cells. Testing this prediction, we restricted Trim24 deficiency to T cells by using a mixed bone marrow chimera system and found that T-cell-intrinsic Trim24 is essential for HDM-mediated airway allergy and antihelminth immunity. Mechanistically, HDM-elicited Trim24(-/-) T cells have reduced expression of many TH2 cytokines and chemokines and were predicted to have compromised IL-1-regulated signaling. Following this prediction, we found that Trim24(-/-) T cells have reduced IL-1 receptor (IL-1R) expression, are refractory to IL-1ß-mediated activation in vitro and in vivo, and fail to respond to IL-1ß-exacerbated airway allergy. Collectively, these data identify a previously unappreciated Trim24-dependent requirement for IL-1R expression on TH2 cells and an important nonredundant role for T-cell-intrinsic Trim24 in TH2-mediated allergy and antihelminth immunity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Proteínas Nucleares / Receptores de Interleucina-1 / Células Th2 / Hipersensibilidad Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Proteínas Nucleares / Receptores de Interleucina-1 / Células Th2 / Hipersensibilidad Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos