Impact of genetic events on innate and inflammasome signaling
| Genetic abnormality . | Gene class . | Mutant gene/ Chromosome alteration . | Innate immune-signaling effect* . | Inflammasome-signaling effect† . | Ref. . |
|---|---|---|---|---|---|
| Somatic mutations | Epigenetic modifiers | TET2 | ↑ IL-6 production via ↓ HDAC2 recruitment; ↑ IL-1β | ↑ Pyroptosis and β-catenin signaling | 28, 30, 40 |
| DNMT3A | ↑ Type 1 IFN production via ↑ HDAC9 expression | 29 | |||
| ASXL1 | ↑ NADPH oxidase ROS; ↑ TLR4, TICAM2 | ↑ Pyroptosis and β-catenin signaling | 31, 40 | ||
| EZH2 | ↑ S100A8/A9 via NF-κB derepression | 25 | |||
| Spliceosomes | SF3B1 | ↑ NF-κB activation via ↓ MAP3K7 | ↑ Pyroptosis and β-catenin signaling | 32, 40 | |
| SRSF2 | ↑ S100A8 and S100A9, DNA-RNA hybrids; ↑ NF-κB activation via caspase 8 isoform | ↑ Pyroptosis and β-catenin signaling | 24, 32, 40 | ||
| U2AF1 | ↑ DNA-RNA hybrids, ATG7 alternate splicing impairing autophagy | ↑ Pyroptosis and β-catenin signaling ; impaired autophagy leading to NLRP3 activation | 40, 43, 44 | ||
| Chromosomal abnormality | N/A | Deletion 5q | Haploinsufficiency: RPS14 ↑ S100A8/A9; miR-145/146 + TIFAB ↑ TRAF6/IRAK1 | ↑ Pyroptosis and β-catenin signaling | 8, 11, 22 |
| Genetic abnormality . | Gene class . | Mutant gene/ Chromosome alteration . | Innate immune-signaling effect* . | Inflammasome-signaling effect† . | Ref. . |
|---|---|---|---|---|---|
| Somatic mutations | Epigenetic modifiers | TET2 | ↑ IL-6 production via ↓ HDAC2 recruitment; ↑ IL-1β | ↑ Pyroptosis and β-catenin signaling | 28, 30, 40 |
| DNMT3A | ↑ Type 1 IFN production via ↑ HDAC9 expression | 29 | |||
| ASXL1 | ↑ NADPH oxidase ROS; ↑ TLR4, TICAM2 | ↑ Pyroptosis and β-catenin signaling | 31, 40 | ||
| EZH2 | ↑ S100A8/A9 via NF-κB derepression | 25 | |||
| Spliceosomes | SF3B1 | ↑ NF-κB activation via ↓ MAP3K7 | ↑ Pyroptosis and β-catenin signaling | 32, 40 | |
| SRSF2 | ↑ S100A8 and S100A9, DNA-RNA hybrids; ↑ NF-κB activation via caspase 8 isoform | ↑ Pyroptosis and β-catenin signaling | 24, 32, 40 | ||
| U2AF1 | ↑ DNA-RNA hybrids, ATG7 alternate splicing impairing autophagy | ↑ Pyroptosis and β-catenin signaling ; impaired autophagy leading to NLRP3 activation | 40, 43, 44 | ||
| Chromosomal abnormality | N/A | Deletion 5q | Haploinsufficiency: RPS14 ↑ S100A8/A9; miR-145/146 + TIFAB ↑ TRAF6/IRAK1 | ↑ Pyroptosis and β-catenin signaling | 8, 11, 22 |
HDAC, histone deacetylase; IFN, interferon; miR, microRNA; N/A, not applicable; NADPH, dihydronicotinamide-adenine dinucleotide phosphate; NLRP3, NOD-like receptor protein 3; Ref., reference(s); ROS, reactive oxygen species; RPS14, ribosomal protein small subunit 14; TICAM2, TIR domain-containing adapter molecule 2; TIFAB, TRAF-interacting protein with forkhead-associated domain B.
Arrows indicate (↑) increase and (↓) decrease.
Arrow (↑) indicates that pyroptosis would be driven by NLRP3 inflammasome activation.