Dendritic Cell RIPK1 Maintains Immune Homeostasis by Preventing Inflammation and Autoimmunity.
Dendritic Cell RIPK1 Maintains Immune Homeostasis by Preventing Inflammation and Autoimmunity.
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DOI：
10.4049/jimmunol.1701229
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发表时间：
2018-01-15
期刊：
影响因子：
--
通讯作者：
Kelliher MA
中科院分区：
文献类型：
--
作者：
O'Donnell JA;Lehman J;Roderick JE;Martinez-Marin D;Zelic M;Doran C;Hermance N;Lyle S;Pasparakis M;Fitzgerald KA;Marshak-Rothstein A;Kelliher MA
Necroptosis is a form of cell death associated with inflammation, however the biological consequences of chronic necroptosis are unknown. Necroptosis is mediated by RIPK1, RIPK3 and MLKL kinases but in hematopoietic cells RIPK1 has anti-inflammatory roles and functions to prevent necroptosis. Here we interrogate the consequences of chronic necroptosis on immune homeostasis by deleting Ripk1 in mouse dendritic cells (DC). We demonstrate that deregulated necroptosis results in systemic inflammation, tissue fibrosis and autoimmunity. We show that inflammation and autoimmunity are prevented upon expression of kinase inactive RIPK1 or deletion of RIPK3 or MLKL. We provide evidence that the inflammation is not driven by microbial ligands, but depends on the release of danger-associated molecular patterns (DAMPs) and MyD88-dependent signaling. Importantly, whilst the inflammation is independent of type I interferon and the nucleic acid sensing TLRs, blocking these pathways rescues the autoimmunity. These mouse genetic studies reveal that chronic necroptosis may underlie human fibrotic and autoimmune disorders.
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DOI：
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发表时间：
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期刊：
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影响因子：
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DOI：
10.1084/jem.20050338
发表时间：
2005-07-18
期刊：
The Journal of experimental medicine
影响因子：
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作者：
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