Cathepsin S is required for murine autoimmune myasthenia gravis pathogenesis.

  • Yang H
  • Kala M
  • Scott B
 et al. 
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Abstract

Because presentation of acetylcholine receptor (AChR) peptides to T cells is critical to the development of myasthenia gravis, we examined the role of cathepsin S (Cat S) in experimental autoimmune myasthenia gravis (EAMG) induced by AChR immunization. Compared with wild type, Cat S null mice were markedly resistant to the development of EAMG, and showed reduced T and B cell responses to AChR. Cat S null mice immunized with immunodominant AChR peptides showed weak responses, indicating failed peptide presentation accounted for autoimmune resistance. A Cat S inhibitor suppressed in vitro IFN-gamma production by lymph node cells from AChR-immunized, DR3-bearing transgenic mice. Because Cat S null mice are not severely immunocompromised, Cat S inhibitors could be tested for their therapeutic potential in EAMG.

Author-supplied keywords

  • Animals
  • Antigen Presentation
  • Antigen Presentation: genetics
  • Antigen-Presenting Cells
  • Antigen-Presenting Cells: immunology
  • Antigen-Presenting Cells: metabolism
  • Autoantibodies
  • Autoantibodies: blood
  • B-Lymphocytes
  • B-Lymphocytes: pathology
  • Cathepsins
  • Cathepsins: antagonists & inhibitors
  • Cathepsins: deficiency
  • Cathepsins: genetics
  • Cathepsins: physiology
  • Cell Differentiation
  • Cell Differentiation: genetics
  • Cell Differentiation: immunology
  • Cell Movement
  • Cell Movement: genetics
  • Cell Movement: immunology
  • Cytokines
  • Cytokines: antagonists & inhibitors
  • Cytokines: biosynthesis
  • Dendritic Cells
  • Dendritic Cells: cytology
  • Dendritic Cells: immunology
  • Down-Regulation
  • Down-Regulation: genetics
  • Down-Regulation: immunology
  • Epitopes, T-Lymphocyte
  • Epitopes, T-Lymphocyte: immunology
  • Female
  • HLA-DR3 Antigen
  • HLA-DR3 Antigen: genetics
  • HLA-DR3 Antigen: immunology
  • HLA-DR3 Antigen: metabolism
  • Humans
  • Immunity, Innate
  • Immunity, Innate: genetics
  • Lymphocyte Activation
  • Lymphocyte Activation: genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Myasthenia Gravis, Autoimmune, Experimental
  • Myasthenia Gravis, Autoimmune, Experimental: enzym
  • Myasthenia Gravis, Autoimmune, Experimental: genet
  • Myasthenia Gravis, Autoimmune, Experimental: immun
  • Peptide Fragments
  • Peptide Fragments: immunology
  • Peptide Fragments: metabolism
  • Receptors, Cholinergic
  • Receptors, Cholinergic: administration & dosage
  • Receptors, Cholinergic: immunology
  • Receptors, Cholinergic: metabolism
  • T-Lymphocytes
  • T-Lymphocytes: immunology
  • T-Lymphocytes: metabolism
  • Torpedo

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Authors

  • Huan Yang

  • Mrinalini Kala

  • Benjamin G Scott

  • Elzbieta Goluszko

  • Harold a Chapman

  • Premkumar Christadoss

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