Table 1.
Selected studies showcasing the use of various cellular models in autoinflammatory disorders
| Disease | Important findings | Cellular model | References |
|---|---|---|---|
| Familial mediterranean fever (FMF) | iPSC‐derived macrophages from FMF patients exhibit inflammatory phenotype | Patient‐derived iPSCs | 90 |
| Neutrophil migration is increased in FMF | Primary neutrophils, HL‐60 | 21 | |
| Investigation of inflammatory features of iPSC‐derived macrophages containing various MEFV variants | Patient‐derived iPSCs | 91 | |
| Neutrophils from active FMF patients show increased migration and activation | Primary neutrophils | 22 | |
| FMF neutrophils transcriptionally and functionally resemble immature activated cells | Primary neutrophils | 23 | |
| miR‐197 is an anti‐inflammatory miRNA that decreases the expression of IL1R1 | THP‐1, SW982 | 61 | |
| Activation of the pyrin inflammasome is related to increased cell migration in monocytes | Primary PBMCs, THP‐1 | 40 | |
| CDC42 is required during pyrin activation | U‐937, THP‐1, HEK293T | 45 | |
| Pyrin activation is less dependent on transcriptional priming in FMF | Primary monocytes, THP‐1, BlaER1 | 46 | |
| TcdB is an activator of the pyrin inflammasome | THP‐1, U‐937, HEK293T | 44 | |
| Steroid hormone catabolites are pyrin inflammasome activators | U‐937 | 56 | |
| PKC inhibitors activate the pyrin inflammasome containing FMF‐associated variants | Primary PBMCs, U‐937 | 57 | |
| Periodic fever, Immunodeficiency and thrombocytopenia syndrome (PFIT) | WDR1 mutations cause an IL‐18–dependent autoinflammatory phenotype | Primary neutrophils, monocyte‐derived dendritic cells, PBMCs; patient‐derived lymphoblastoid cell line (LCL), HEK293T | 20 |
| WDR1 mutations effect immunological synapse formation and B‐cell development | Primary PBMCs, neutrophils, T‐cells, patient‐derived LCL | 12 | |
| Pyrin‐associated autoinflammatory disease (PAAND) | PAAND neutrophils display an activated phenotype and increased phagocytosis | Primary neutrophils | 23 |
| Cryopyrin‐associated periodic syndrome (CAPS) | Non‐mutant cells from a somatic mosaic CINCA syndrome patient may contribute to inflammatory phenotype | Patient‐derived iPSCs | 95 |
| NLRP3 mutation disrupts chondrogenesis via SOX9 activation independent of inflammatory effect | Patient‐derived iPSCs | 97 | |
| Phenotypic characterisation of iPSC‐derived cells from a NOMID patient led to the identification of the disease‐causing mutation | Patient‐derived iPSCs | 96 | |
| A novel TRAPS mutation increases NF‐KB activity, cytokine production and mtROS production | Primary PBMCs, HEK293 | 63 | |
| iPSC‐derived macrophages from a NOMID patient used to test compounds able to inhibit IL‐1β | Patient‐derived iPSCs | 104 | |
| Cold exposure promotes NLRP3 aggregation and activation | THP‐1, HeLa | 42 | |
| Functional investigation of different NLRP3 variants | Primary PBMCs, U‐937 | 59 | |
| Proteasome‐associated autoinflammatory syndrome (PRAAS) | Proteasome assembly dysfunction and resulting IFN signature are defining characteristics of CANDLE/PRAAS | Primary fibroblasts, keratinocytes, B‐cells, HeLa | 25 |
| POMP mutation leads to autoinflammation via dysfunction of the inflammasome and activation of the ER stress pathway | Primary fibroblasts, patient‐derived LCL, HEK293T | 13 | |
| POMP8 mutations lead to ubiquitinated protein accumulation, ROS production and type I IFN signature | Patient‐derived iPSCs | 103 | |
| PAC2 mutation leads to decreased proteasome activity | Primary fibroblasts, HeLa | 26 | |
| iPSC‐derived macrophages from a PRAAS patient used to test potential therapeutic compounds | Patient‐derived iPSCs | 105 | |
| Blau syndrome | Blau syndrome macrophages demonstrate an IFN‐ɣ dependent exaggerated inflammatory response to NOD2 ligands | Patient‐derived iPSCs | 101 |
| Evaluation of NF‐KB activation caused by various NOD2 mutations | HEK293 | 65 | |
| Anti‐inflammatory effect of anti‐TNF treatment on patient‐derived macrophages in terms of gene expression profiles is eliminated in iPSC‐derived macrophages | Patient‐derived iPSCs | 100 | |
| Autoinflammation, antibody deficiency, and immune dysregulation (APLAID) | Enhanced activity of Phospholipase Cɣ2 underlies the pathogenesis of PLAID | Primary PBMCs, COS‐7 | 66 |
| Coatomer protein complex, subunit alpha gene (COPA) syndrome | COPA syndrome is caused by defective retrograde ER‐Golgi transport | HEK293T, patient‐derived LCL | 14 |
| Autoinflammation, panniculitis and dermatosis syndrome | Mutations of OTULIN gene lead to aberrant ubiquitination of proteins in the NF‐KB signalling pathway | Primary fibroblasts, primary PBMCs, HEK293 | 29 |
| Early‐onset macrophage activation syndrome (MAS) | NLRC4 mutations lead to inflammatory cytokine production and cell death | THP‐1, HEK293T | 43 |
| Haploinsufficiency of A20 (HA20) | Identification of novel mutations of TNFAIP3 as the causative factor of autoinflammation in suspected cases of HA20 | HEK293 | 64 |
| Primary PBMCs, THP‐1 | 41 | ||
| NEMO deleted exon 5 autoinflammatory syndrome (NDAS) | Detailed characterisation of the molecular pathogenesis of three patients with autoinflammatory disease harbouring a NEMO‐Δex5 mutation | Primary fibroblasts, primary PBMCs, HEK293T, THP‐1, Jurkat, patient‐derived iPSCs | 27 |
| Cleavage‐resistant RIPK1‐induced autoinflammatory syndrome (CRIA syndrome) | Caspase‐8 resistant RIPK1 variants lead to increased necroptosis and autoinflammation | HEK293T, HeLa | 67 |
| Deficiency of adenosine deaminase 2 (DADA2) | ADA2 KO U‐937 cells recapitulate disease phenotype in terms of IL‐6 and TNF secretion, lentiviral correction of ADA2 alleviates inflammation | Primary PBMCs, primary CD34+ cells, U‐937 | 54 |
| Transcriptomic analysis of the pathogenicity of different ADA2 variants | Primary PBMCs, HEK293, U‐937 | 55 | |
| VEXAS syndrome | Functional analysis of UBA1 mutations in VEXAS syndrome | THP‐1, U‐937 | 58 |
| Neonatal onset of pancytopenia, autoinflammation, rash and episodes of haemophagocytic lymphohistiocytosis (NOCARH) syndrome | Mutant CDC42 accumulated in the Golgi apparatus leads to pyrin inflammasome activation | Patient‐derived iPSCs, primary PBMCs, THP‐1, HEK293T, COS‐1 | 92 |
| Multiple self‐healing palmoplantar carcinoma (MSPC), Familial keratosis lichenoides chronica (FKLC) | Gain‐of‐function mutations of NLRP1 lead to skin inflammatory phenotypes | Primary keratinocytes, primary fibroblasts, THP‐1, HEK293T | 34 |
| Juvenile recurrent respiratory papillomatosis | Activation of mutant NLRP1 underlies juvenile recurrent respiratory papillomatosis | Primary keratinocytes, HEK293T | 35 |
| DPP9 deficiency | DPP9 deficiency leads to spontaneous activation of the NLRP1 inflammasome | Primary keratinocytes, primary fibroblasts, HEK293T | 36 |