title: TIRC7 and HLA-DR axis contributes to inflammation in multiple sclerosis.
abstract: Interactions between TIRC7 (a novel seven-transmembrane receptor on activated lymphocytes) and its ligand HLA-DR might be involved in the inflammatory process in multiple sclerosis (MS).
  
  
  
  Methods comprised immunohistochemistry and microscopy on archival MS autopsies, proliferation-, cytokine-, and surface-staining assays using peripheral blood lymphocytes (PBLs) from MS patients and an in vitro model.
  
  
  
  TIRC7 was expressed in brain-infiltrating lymphocytes and strongly correlated with disease activity in MS. TIRC7 expression was reduced in T cells and induced in B cells in PBLs obtained from MS patients. After ex vivo activation, T cell expression of TIRC7 was restored in patients with active MS disease. The interaction of TIRC7(+) T lymphocytes with cells expressing HLA-DR on their surface led to T cell proliferation and activation whereas an anti-TIRC7 mAb preventing interactions with its ligand inhibited proliferation and Th1 and Th17 cytokine expression in T cells obtained from MS patients and in myelin basic protein-specific T cell clone.
  
  
  
  Our findings suggest that TIRC7 is involved in inflammation in MS and anti-TIRC7 mAb can prevent immune activation via selective inhibition of Th1- and Th17-associated cytokine expression. This targeting approach may become a novel treatment option for MS.
authors: Division of Neuroimmunology, Centre for Brain Research, Medical University of Vienna, Austria Department of Neurosurgery, Medical University of Vienna, Austria josa.frischer@meduniwien.ac.at.
authors: J M
authors: JM
authors: Frischer
authors: Clinical Department of Neurology, Innsbruck Medical University, Austria.
authors: M
authors: M
authors: Reindl
authors: Clinical Department of Neurology, Innsbruck Medical University, Austria.
authors: B
authors: B
authors: Künz
authors: Clinical Department of Neurology, Innsbruck Medical University, Austria.
authors: T
authors: T
authors: Berger
authors: Neurology - Bonn, Germany.
authors: S
authors: S
authors: Schmidt
authors: Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors: E L
authors: EL
authors: Milford
authors: Department of Neurosurgery, Medical University of Vienna, Austria.
authors: E
authors: E
authors: Knosp
authors: Division of Neuroimmunology, Centre for Brain Research, Medical University of Vienna, Austria.
authors: H
authors: H
authors: Lassmann
authors: Institute for Medical Immunology, Charité, Germany.
authors: N
authors: N
authors: Utku
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001344:Autopsy; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D012720:Severity of Illness Index; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D016207:Cytokines; D006684:HLA-DR Antigens; D018836:Inflammation Mediators; C472421:TCIRG1 protein, human; D025262:Vacuolar Proton-Translocating ATPases
keywords: Multiple sclerosis; immunology