Fas-independent T-cell apoptosis by dendritic cells controls autoimmune arthritis in MRL/lpr mice.
<h4>Background</h4>Although autoimmunity in MRL/lpr mice occurs due to a defect in Fas-mediated cell death of T cells, the role of Fas-independent apoptosis in pathogenesis has rarely been investigated. We have recently reported that receptor activator of nuclear factor (NF)-κB ligand (R...
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2012
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oai:doaj.org-article:c8c0b3f4099249fa933d03ecde6e3f502021-11-18T08:05:14ZFas-independent T-cell apoptosis by dendritic cells controls autoimmune arthritis in MRL/lpr mice.1932-620310.1371/journal.pone.0048798https://doaj.org/article/c8c0b3f4099249fa933d03ecde6e3f502012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23300516/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Although autoimmunity in MRL/lpr mice occurs due to a defect in Fas-mediated cell death of T cells, the role of Fas-independent apoptosis in pathogenesis has rarely been investigated. We have recently reported that receptor activator of nuclear factor (NF)-κB ligand (RANKL)-activated dendritic cells (DCs) play a key role in the pathogenesis of rheumatoid arthritis (RA) in MRL/lpr mice. We here attempted to establish a new therapeutic strategy with RANKL-activated DCs in RA by controlling apoptosis of peripheral T cells. Repeated transfer of RANKL-activated DCs into MRL/lpr mice was tested to determine whether this had a therapeutic effect on autoimmunity.<h4>Methods and finding</h4>Cellular and molecular mechanisms of Fas-independent apoptosis of T cells induced by the DCs were investigated by in vitro and in vivo analyses. We demonstrated that repeated transfers of RANKL-activated DCs into MRL/lpr mice resulted in therapeutic effects on RA lesions and lymphoproliferation due to declines of CD4(+) T, B, and CD4(-)CD8(-) double negative (DN) T cells. We also found that the Fas-independent T-cell apoptosis was induced by a direct interaction between tumor necrosis factor (TNF)-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2) on T cells and TRAIL on Fas-deficient DCs in MRL/lpr mice.<h4>Conclusion</h4>These results strongly suggest that a novel Fas-independent apoptosis pathway in T cells maintains peripheral tolerance and thus controls autoimmunity in MRL/lpr mice.Takashi IzawaTomoyuki KondoMie KurosawaRitsuko OuraKazuma MatsumotoEiji TanakaAkiko YamadaRieko ArakakiYasusei KudoYoshio HayashiNaozumi IshimaruPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e48798 (2012) |
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Medicine R Science Q Takashi Izawa Tomoyuki Kondo Mie Kurosawa Ritsuko Oura Kazuma Matsumoto Eiji Tanaka Akiko Yamada Rieko Arakaki Yasusei Kudo Yoshio Hayashi Naozumi Ishimaru Fas-independent T-cell apoptosis by dendritic cells controls autoimmune arthritis in MRL/lpr mice. |
| description |
<h4>Background</h4>Although autoimmunity in MRL/lpr mice occurs due to a defect in Fas-mediated cell death of T cells, the role of Fas-independent apoptosis in pathogenesis has rarely been investigated. We have recently reported that receptor activator of nuclear factor (NF)-κB ligand (RANKL)-activated dendritic cells (DCs) play a key role in the pathogenesis of rheumatoid arthritis (RA) in MRL/lpr mice. We here attempted to establish a new therapeutic strategy with RANKL-activated DCs in RA by controlling apoptosis of peripheral T cells. Repeated transfer of RANKL-activated DCs into MRL/lpr mice was tested to determine whether this had a therapeutic effect on autoimmunity.<h4>Methods and finding</h4>Cellular and molecular mechanisms of Fas-independent apoptosis of T cells induced by the DCs were investigated by in vitro and in vivo analyses. We demonstrated that repeated transfers of RANKL-activated DCs into MRL/lpr mice resulted in therapeutic effects on RA lesions and lymphoproliferation due to declines of CD4(+) T, B, and CD4(-)CD8(-) double negative (DN) T cells. We also found that the Fas-independent T-cell apoptosis was induced by a direct interaction between tumor necrosis factor (TNF)-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2) on T cells and TRAIL on Fas-deficient DCs in MRL/lpr mice.<h4>Conclusion</h4>These results strongly suggest that a novel Fas-independent apoptosis pathway in T cells maintains peripheral tolerance and thus controls autoimmunity in MRL/lpr mice. |
| format |
article |
| author |
Takashi Izawa Tomoyuki Kondo Mie Kurosawa Ritsuko Oura Kazuma Matsumoto Eiji Tanaka Akiko Yamada Rieko Arakaki Yasusei Kudo Yoshio Hayashi Naozumi Ishimaru |
| author_facet |
Takashi Izawa Tomoyuki Kondo Mie Kurosawa Ritsuko Oura Kazuma Matsumoto Eiji Tanaka Akiko Yamada Rieko Arakaki Yasusei Kudo Yoshio Hayashi Naozumi Ishimaru |
| author_sort |
Takashi Izawa |
| title |
Fas-independent T-cell apoptosis by dendritic cells controls autoimmune arthritis in MRL/lpr mice. |
| title_short |
Fas-independent T-cell apoptosis by dendritic cells controls autoimmune arthritis in MRL/lpr mice. |
| title_full |
Fas-independent T-cell apoptosis by dendritic cells controls autoimmune arthritis in MRL/lpr mice. |
| title_fullStr |
Fas-independent T-cell apoptosis by dendritic cells controls autoimmune arthritis in MRL/lpr mice. |
| title_full_unstemmed |
Fas-independent T-cell apoptosis by dendritic cells controls autoimmune arthritis in MRL/lpr mice. |
| title_sort |
fas-independent t-cell apoptosis by dendritic cells controls autoimmune arthritis in mrl/lpr mice. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/c8c0b3f4099249fa933d03ecde6e3f50 |
| work_keys_str_mv |
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| _version_ |
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