| First Author | Mc Guire C | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 6 | Pages | 2896-903 |
| PubMed ID | 23401595 | Mgi Jnum | J:193681 |
| Mgi Id | MGI:5469213 | Doi | 10.4049/jimmunol.1201351 |
| Citation | Mc Guire C, et al. (2013) Paracaspase MALT1 Deficiency Protects Mice from Autoimmune-Mediated Demyelination. J Immunol 190(6):2896-903 |
| abstractText | The paracaspase MALT 1 is a major player in lymphocyte activation and proliferation. MALT1 mediates Ag-induced signaling to the transcription factor NF-kappaB 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. |
