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- Publisher Website: 10.1073/pnas.1323166111
- Scopus: eid_2-s2.0-84892931838
- PMID: 24398517
- WOS: WOS:000329928400050
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Article: Toso controls encephalitogenic immune responses by dendritic cells and regulatory T cells
Title | Toso controls encephalitogenic immune responses by dendritic cells and regulatory T cells |
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Authors | |
Keywords | Inflammation Th1/Th17 cells |
Issue Date | 2014 |
Citation | Proceedings of the National Academy of Sciences of the United States of America, 2014, v. 111, n. 3, p. 1060-1065 How to Cite? |
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. |
Persistent Identifier | http://hdl.handle.net/10722/292235 |
ISSN | 2023 Impact Factor: 9.4 2023 SCImago Journal Rankings: 3.737 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Brenner, Dirk | - |
dc.contributor.author | Brüstle, Anne | - |
dc.contributor.author | Lin, Gloria H.Y. | - |
dc.contributor.author | Lang, Philipp A. | - |
dc.contributor.author | Duncan, Gordon S. | - |
dc.contributor.author | Knobbe-Thomsen, Christiane B. | - |
dc.contributor.author | Paul, Michael ST | - |
dc.contributor.author | Reardon, Colin | - |
dc.contributor.author | Tusche, Michael W. | - |
dc.contributor.author | Snow, Bryan | - |
dc.contributor.author | Hamilton, Sara R. | - |
dc.contributor.author | Pfefferle, Aline | - |
dc.contributor.author | Gilani, Syed O. | - |
dc.contributor.author | Ohashi, Pamela S. | - |
dc.contributor.author | Lang, Karl S. | - |
dc.contributor.author | Mak, Tak W. | - |
dc.date.accessioned | 2020-11-17T14:56:03Z | - |
dc.date.available | 2020-11-17T14:56:03Z | - |
dc.date.issued | 2014 | - |
dc.identifier.citation | Proceedings of the National Academy of Sciences of the United States of America, 2014, v. 111, n. 3, p. 1060-1065 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | http://hdl.handle.net/10722/292235 | - |
dc.description.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. | - |
dc.language | eng | - |
dc.relation.ispartof | Proceedings of the National Academy of Sciences of the United States of America | - |
dc.subject | Inflammation | - |
dc.subject | Th1/Th17 cells | - |
dc.title | Toso controls encephalitogenic immune responses by dendritic cells and regulatory T cells | - |
dc.type | Article | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1073/pnas.1323166111 | - |
dc.identifier.pmid | 24398517 | - |
dc.identifier.pmcid | PMC3903229 | - |
dc.identifier.scopus | eid_2-s2.0-84892931838 | - |
dc.identifier.volume | 111 | - |
dc.identifier.issue | 3 | - |
dc.identifier.spage | 1060 | - |
dc.identifier.epage | 1065 | - |
dc.identifier.eissn | 1091-6490 | - |
dc.identifier.isi | WOS:000329928400050 | - |
dc.identifier.issnl | 0027-8424 | - |