The Spliceosomal Phosphopeptide P140 Controls the Lupus Disease by Interacting with the HSC70 Protein and via a Mechanism Mediated by γδ T Cells
| Autor: | Jean-Marc Strub, Nicolas Schall, Jean-Paul Briand, Alain Van Dorsselaer, Manh Thong Cung, Sylviane Muller, Nicolas Page, Marion Decossas, Marc Quinternet, Olivier Chaloin |
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| Přispěvatelé: | Immunologie et chimie thérapeutiques (ICT), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Spectrométrie de Masse BioOrganique [Strasbourg] (LSMBO), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie Physique Macromoléculaire (LCPM), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Mice
Inbred MRL lpr T-Lymphocytes Immunology/Innate Immunity Immunology/Immunomodulation Fluorescent Antibody Technique Apoptosis medicine.disease_cause T-Lymphocytes Regulatory Autoimmunity Interleukin 21 Mice 0302 clinical medicine immune system diseases Biochemistry/Cell Signaling and Trafficking Structures Cytotoxic T cell Lupus Erythematosus Systemic Biochemistry/Biomacromolecule-Ligand Interactions 0303 health sciences B-Lymphocytes Multidisciplinary ZAP70 Receptors Antigen T-Cell gamma-delta 3. Good health medicine.anatomical_structure 030220 oncology & carcinogenesis Medicine Biochemistry/Drug Discovery Research Article T cell Science Immunology/Autoimmunity Down-Regulation Biology Models Biological Ribonucleoprotein U1 Small Nuclear 03 medical and health sciences Antigen medicine Animals B cell Rheumatology/Autoimmunity Autoimmune and Inflammatory Diseases 030304 developmental biology Binding Sites HSC70 Heat-Shock Proteins [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy Surface Plasmon Resonance Molecular biology Peptide Fragments Peripheral blood lymphocyte Rheumatology/Systemic Lupus Erythematosos Immunology/Immune Response |
| Zdroj: | PLoS ONE PLoS ONE, Vol 4, Iss 4, p e5273 (2009) PLoS ONE, Public Library of Science, 2009, 4 (4), pp.e5273. ⟨10.1371/journal.pone.0005273⟩ |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0005273⟩ |
| Popis: | International audience; The phosphopeptide P140 issued from the spliceosomal U1-70K snRNP protein is recognized by lupus CD4(+) T cells, transiently abolishes T cell reactivity to other spliceosomal peptides in P140-treated MRL/lpr mice, and ameliorates their clinical features. P140 modulates lupus patients' T cell response ex vivo and is currently included in phase IIb clinical trials. Its underlying mechanism of action remains elusive. Here we show that P140 peptide binds a unique cell-surface receptor, the constitutively-expressed chaperone HSC70 protein, known as a presenting-protein. P140 induces apoptosis of activated MRL/lpr CD4(+) T cells. In P140-treated mice, it increases peripheral blood lymphocyte apoptosis and decreases B cell, activated T cell, and CD4(-)CD8(-)B220(+) T cell counts via a specific mechanism strictly depending on gammadelta T cells. Expression of inflammation-linked genes is rapidly regulated in CD4(+) T cells. This work led us to identify a powerful pathway taken by a newly-designed therapeutic peptide to immunomodulate lupus autoimmunity. |
| Databáze: | OpenAIRE |
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