Item request has been placed! ×
Item request cannot be made. ×
loading  Processing Request

A non-conserved amino acid variant regulates differential signalling between human and mouse CD28

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
اقرأ أكثر حفظ في قائمتي
  • معلومة اضافية
    • Contributors:
      Department of Biology and Biotechnology "Charles Darwin"; Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti; Pasteur Network (Réseau International des Instituts Pasteur)-Pasteur Network (Réseau International des Instituts Pasteur)-Università degli Studi di Roma "La Sapienza" = Sapienza University Rome (UNIROMA); Università degli Studi di Roma "La Sapienza" = Sapienza University Rome (UNIROMA); Department of Molecular Medicine; Pasteur Network (Réseau International des Instituts Pasteur); Istituto Superiore di Sanità = National Institute of Health (ISS); Centre de Recherche en Cancérologie de Marseille (CRCM); Aix Marseille Université (AMU)-Institut Paoli-Calmettes (IPC); Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Immunotech-Beckman Coulter; Immunotech; Centro de Biología Molecular Severo Ochoa Madrid (CBMSO); Consejo Superior de Investigaciones Cientificas España = Spanish National Research Council Spain (CSIC)-Universidad Autónoma de Madrid (UAM); The work was supported by: “Progetto Ateneo” (Sapienza University of Rome, Italy) and Multiple Sclerosis Italian Foundation (FISM 2016/R/29).
    • بيانات النشر:
      CCSD
      Nature Publishing Group
    • الموضوع:
      2018
    • Collection:
      Réseau International des Instituts Pasteur, Paris: HAL-RIIP
    • نبذة مختصرة :
      International audience ; CD28 superagonistic antibodies (CD28SAb) can preferentially activate and expand immu-nosuppressive regulatory T cells (Treg) in mice. However, pre-clinical trials assessing CD28SAbs for the therapy of autoimmune diseases reveal severe systemic inflammatory response syndrome in humans, thereby implying the existence of distinct signalling abilities between human and mouse CD28. Here, we show that a single amino acid variant within the C-terminal proline-rich motif of human and mouse CD28 (P 212 in human vs. A 210 in mouse) regulates CD28-induced NF-κB activation and pro-inflammatory cytokine gene expression. Moreover, this Y 209 APP 212 sequence in humans is crucial for the association of CD28 with the Nck adaptor protein for actin cytoskeleton reorganisation events necessary for CD28 autonomous signalling. This study thus unveils different outcomes between human and mouse CD28 signalling to underscore the importance of species difference when transferring results from preclinical models to the bedside.
    • Relation:
      info:eu-repo/semantics/altIdentifier/pmid/29540686; PUBMED: 29540686; PUBMEDCENTRAL: PMC5852078
    • الرقم المعرف:
      10.1038/s41467-018-03385-8
    • الدخول الالكتروني :
      https://hal.science/hal-01772994
      https://hal.science/hal-01772994v1/document
      https://hal.science/hal-01772994v1/file/s41467-018-03385-8.pdf
      https://doi.org/10.1038/s41467-018-03385-8
    • Rights:
      http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess
    • الرقم المعرف:
      edsbas.A7CD436D