Cell Death-Related Ubiquitin Modifications in Inflammatory Syndromes: From Mice to Men
Abstract
:1. Introduction
2. TNFR1-Signalling Pathway
3. LUBAC
4. OTULIN
5. A20
6. XIAP
7. Omics
8. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Mouse | Human | |||
---|---|---|---|---|
Gene | Tissue | Phenotype | Mutation | Phenotype |
Hoip/ Hoil-1 | Full body deletion | -Embryonic lethality -Excessive endothelial cell death [39,43] | Deletion/ nonsense/ missense | -Autoinflammation (e.g., abdominal pain) -Immunodeficiency (recurrent bacterial infections) -Amylopectin-like deposit in the muscle -Cardiomyopathy -Progressive muscular weakness -Immune cells hyperresponsive to IL-1β stimulation -Delayed NF-kB activation in non-immune cells -Lymphopenia [53,54,55,56] |
Skin-specific deletion | -Excessive keratinocyte death -Severe skin inflammation [44,45] | |||
T cell-specific deletion | -Severe T cell depletion -Delayed NF-κB activation in TNF- and TCR-induced-signalling pathways [47] | |||
Hoip | Liver-specific deletion | -Hepatocyte death-driven inflammation -Hepatocellular carcinoma [46] | ||
B cell-specific deletion | -Impaired CD40 signalling and antibody production [48] | |||
Hoil-1 | Catalytic inactive (Full body) | -Increased NF-κB activation -Protection from cell death -Glycogen deposition [51] | ||
Sharpin | Full body mutation | -Chronic proliferative dermatitis -Liver inflammation -Peyer’s patches loss -Splenomegaly [40] | Missense | Risk factor for LOAD (Late-onset Alzheimer disease) [58,59] |
Otulin | Full body deletion | -Embryonic lethality -Loss of vascularization [60] | Loss of function | -ORAS (OTULIN-related autoinflammatory syndrome) or Otulipenia -Systemic sterile inflammation (e.g., joint swelling, prolonged fever, diarrhoea, panniculitis) -Developmental delay -Increased linear ubiquitination and NF-κB activation -Infliximab (monoclonal anti-TNF antibody) ameliorates the symptoms [61,62,63] |
Full body conditional deletion | Decreased survival [61] | |||
Myeloid-cell specific deletion | -Severe acute systemic inflammation -NF-κB hyperactivation -Excessive cytokine production [61] | |||
Catalytic inactivation (full body) | -Embryonic lethality -Deregulated endothelial cell death [64] | |||
Skin-specific deletion | -Deregulated keratinocyte death -Severe skin inflammation [65,66] | |||
Liver-specific deletion | -TNFR1-driven hepatocyte death -Compensatory proliferation -Hepatocellular carcinoma [67] | |||
A20 | Full body deletion | -Perinatal lethality [68] -Cell death-dependent multiorgan inflammation (e.g., liver, kidneys, joints) | Nonsense | -Early onset systemic inflammation (e.g., arthritis, oral and genital ulcers, SLE-like disease, central nervous system vasculitis) -Patients’ derived immune cells have elevated cytokine levels, are hyperresponsive to inflammasome activation. Fibroblasts have increased NF-kB activation following TNF stimulation [69,70,71,72,73,74,75] |
Myeloid cell-specific deletion | -Cell death-dependent joint inflammation [76] | |||
ZnF7 mutation (full body) | -Cell death-dependent joint inflammation [76] | |||
Xiap | Full body deletion | -Low grade ileal inflammation, TNFR1- and TNFR2-dependent -Increased sensitivity to pathogenic bacterial strain -Cell death-dependent reduction in Paneth cells and dendritic cells -Cell death is the trigger of ileal inflammation [77,78] | Deletion/ insertion/ nonsense/ missense/ frameshift/ intronic | -Familia hemophagocytic lymphohystiocystiosis (FHLH) or XLP2 -High risk IBD -Excessive activation of macrophages and dendritic cells following EBV infection [79,80] |
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Peltzer, N.; Annibaldi, A. Cell Death-Related Ubiquitin Modifications in Inflammatory Syndromes: From Mice to Men. Biomedicines 2022, 10, 1436. https://doi.org/10.3390/biomedicines10061436
Peltzer N, Annibaldi A. Cell Death-Related Ubiquitin Modifications in Inflammatory Syndromes: From Mice to Men. Biomedicines. 2022; 10(6):1436. https://doi.org/10.3390/biomedicines10061436
Chicago/Turabian StylePeltzer, Nieves, and Alessandro Annibaldi. 2022. "Cell Death-Related Ubiquitin Modifications in Inflammatory Syndromes: From Mice to Men" Biomedicines 10, no. 6: 1436. https://doi.org/10.3390/biomedicines10061436
APA StylePeltzer, N., & Annibaldi, A. (2022). Cell Death-Related Ubiquitin Modifications in Inflammatory Syndromes: From Mice to Men. Biomedicines, 10(6), 1436. https://doi.org/10.3390/biomedicines10061436