title: Paracaspase MALT1 deficiency protects mice from autoimmune-mediated demyelination.
abstract: The paracaspase MALT 1 is a major player in lymphocyte activation and proliferation. MALT1 mediates Ag-induced signaling to the transcription factor NF-κB by functioning both as a scaffold protein and cysteine protease. We studied the role of MALT1 in the development of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. MALT1-knockout mice did not develop any clinical symptoms of EAE. In addition, lymphocyte and macrophage infiltration into the spinal cord was absent in MALT1-knockout mice, as were demyelination and proinflammatory gene expression. Adoptive transfer experiments showed that MALT1 deficiency in splenocytes is sufficient for EAE resistance. Moreover, autoreactive T cell activation was severely impaired in MALT1-deficient T cells, suggesting the inability of MALT1-deficient effector T cells to induce demyelinating inflammation in the CNS. Finally, the MALT1 substrates A20 and CYLD were completely processed in wild-type T cells during EAE, which was partially impaired in MALT1-deficient T cells, suggesting a contribution of MALT1 proteolytic activity in T cell activation and EAE development. Together, our data indicate that MALT1 may be an interesting therapeutic target in the treatment of multiple sclerosis.
authors: Department for Molecular Biomedical Research, Unit of Molecular Signal Transduction in Inflammation, VIB, B-9052 Ghent, Belgium.
authors: Conor
authors: C
authors: Mc Guire
authors: Peter
authors: P
authors: Wieghofer
authors: Lynn
authors: L
authors: Elton
authors: David
authors: D
authors: Muylaert
authors: Marco
authors: M
authors: Prinz
authors: Rudi
authors: R
authors: Beyaert
authors: Geert
authors: G
authors: van Loo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015551:Autoimmunity / Q000235:genetics; D020169:Caspases / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D003711:Demyelinating Diseases / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000201:enzymology* / Q000235:genetics / Q000276:immunology*; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D009363:Neoplasm Proteins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology
chemical_list: D009363:Neoplasm Proteins; D020169:Caspases; C498509:Malt1 protein, mouse; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein