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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | St Paul, Michael Reardon, Colin Tusche, Michael W. Gilani, Syed O. Ohashi, Pamela S. Lang, Karl S. Lin, Gloria H. Y. Snow, Bryan Brüstle, Anne Knobbe-thomsen, Christiane B. Mak, Tak W. Lang, Philipp A. Hamilton, Sara R. Pfefferle, Aline Brenner, Dirk Duncan, Gordon S. |
| Description | Author Affiliation: Brenner D ( The Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, ON, Canada M5G 2C1.); |
| Abstract | The ability to mount a strong immune response against pathogens is crucial for mammalian survival. However, excessive and uncontrolled immune reactions can lead to autoimmunity. Unraveling how the reactive versus tolerogenic state is controlled might point toward novel therapeutic strategies to treat autoimmune diseases. The surface receptor Toso/Faim3 has been linked to apoptosis, IgM binding, and innate immune responses. In this study, we used Toso-deficient mice to investigate the importance of Toso in tolerance and autoimmunity. We found that Toso(-/-) mice do not develop severe experimental autoimmune encephalomyelitis (EAE), a mouse model for the human disease multiple sclerosis. Toso(-/-) dendritic cells were less sensitive to Toll-like receptor stimulation and induced significantly lower levels of disease-associated inflammatory T-cell responses. Consistent with this observation, the transfer of Toso(-/-) dendritic cells did not induce autoimmune diabetes, indicating their tolerogenic potential. In Toso(-/-) mice subjected to EAE induction, we found increased numbers of regulatory T cells and decreased encephalitogenic cellular infiltrates in the brain. Finally, inhibition of Toso activity in vivo at either an early or late stage of EAE induction prevented further disease progression. Taken together, our data identify Toso as a unique regulator of inflammatory autoimmune responses and an attractive target for therapeutic intervention. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 3 |
| Volume Number | 111 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2014-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Carrier Proteins Metabolism Dendritic Cells Cytology Encephalomyelitis, Autoimmune, Experimental Immunology Membrane Proteins T-Lymphocytes, Regulatory Animals Cell Differentiation Cell Proliferation Cytokines Therapy Gene Expression Regulation HEK293 Cells Immunohistochemistry Inflammation Mice Mice, Inbred C57BL Mice, Knockout Th1 Cells Th17 Cells Time Factors Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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