Correction: Dendritic Cell RIPK1 Maintains Immune Homeostasis by Preventing Inflammation and Autoimmunity
| Autor: | Justine E. Roderick, Michelle A. Kelliher, Ciara G. Doran, Matija Zelic, Joanne A. O’Donnell, Dalia Martinez-Marin, Manolis Pasparakis, Katherine A. Fitzgerald, Stephen Lyle, Jesse Lehman, Nicole Hermance, Ann Marshak-Rothstein |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0106 biological sciences
0301 basic medicine business.industry Immunology chemical and pharmacologic phenomena Inflammation Dendritic cell 030108 mycology & parasitology medicine.disease_cause 01 natural sciences Article Autoimmunity 010602 entomology 03 medical and health sciences RIPK1 Immunology and Allergy Medicine Immune homeostasis medicine.symptom business |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 200(8) |
| ISSN: | 1550-6606 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|