Diverse Roles of NETosis in the Pathogenesis of Lupus
NETosis is a form of neutrophil cell death during which extracellular fibrillary structures composed of cytosolic and granule proteins assembled on scaffolds of decondensed chromatin, called neutrophil extracellular traps (NETs), are released. NETs normally contribute to host immune defense. Accumul...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-05-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.895216/full |
| _version_ | 1818551155659112448 |
|---|---|
| author | Meiying Wang Meiying Wang Tatsuya Ishikawa Yupeng Lai Dhiraj Nallapothula Ram Raj Singh Ram Raj Singh Ram Raj Singh Ram Raj Singh |
| author_facet | Meiying Wang Meiying Wang Tatsuya Ishikawa Yupeng Lai Dhiraj Nallapothula Ram Raj Singh Ram Raj Singh Ram Raj Singh Ram Raj Singh |
| author_sort | Meiying Wang |
| collection | DOAJ |
| description | NETosis is a form of neutrophil cell death during which extracellular fibrillary structures composed of cytosolic and granule proteins assembled on scaffolds of decondensed chromatin, called neutrophil extracellular traps (NETs), are released. NETs normally contribute to host immune defense. Accumulating evidence implicates aberrant NET production and/or reduced NET clearance, along with alterations of molecules involved in NETosis pathway, in humans and animals with lupus. The extruded nuclear antigens released by NET are a source of autoantigens, which can contribute to the breakdown of self-tolerance in lupus. Excessive NET can also promote the production of pro-inflammatory cytokine interferon-α, elicit direct cytotoxic effect on various renal cells, and cause capillary necrosis and podocyte loss. Additionally, NET can induce endothelial-to-mesenchymal transdifferentiation, which can promote activated myofibroblasts leading to extracellular matrix production. Thus, aberrant NETosis can play diverse roles, including autoantibody production, inflammation, and tissue damage, at different stages of lupus pathogenesis. Evidence suggests that treatments currently used in lupus may reduce NETosis, suggesting a potential utility of targeting NETosis to treat lupus. In fact, several approaches are being experimented to therapeutically target pathways of NETosis. Future studies should precisely delineate distinct roles of NETosis at different stages of lupus pathogenesis in humans, which would offer a rational basis for NETosis-targeting treatments in the clinic. |
| first_indexed | 2024-12-12T08:56:06Z |
| format | Article |
| id | doaj.art-079113e8f8f647569a3604aa396d4ba3 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T08:56:06Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-079113e8f8f647569a3604aa396d4ba32022-12-22T00:29:59ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-05-011310.3389/fimmu.2022.895216895216Diverse Roles of NETosis in the Pathogenesis of LupusMeiying Wang0Meiying Wang1Tatsuya Ishikawa2Yupeng Lai3Dhiraj Nallapothula4Ram Raj Singh5Ram Raj Singh6Ram Raj Singh7Ram Raj Singh8Autoimmunity and Tolerance Laboratory, Division of Rheumatology, Department of Medicine, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, United StatesDepartment of Rheumatology and Immunology, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, ChinaAutoimmunity and Tolerance Laboratory, Division of Rheumatology, Department of Medicine, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, United StatesDepartment of Rheumatology and Immunology, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, ChinaAutoimmunity and Tolerance Laboratory, Division of Rheumatology, Department of Medicine, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, United StatesAutoimmunity and Tolerance Laboratory, Division of Rheumatology, Department of Medicine, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA, United StatesDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United StatesMolecular Toxicology Interdepartmental Program, David Geffen School of Medicine at UCLA, Los Angeles, CA, United StatesJonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, United StatesNETosis is a form of neutrophil cell death during which extracellular fibrillary structures composed of cytosolic and granule proteins assembled on scaffolds of decondensed chromatin, called neutrophil extracellular traps (NETs), are released. NETs normally contribute to host immune defense. Accumulating evidence implicates aberrant NET production and/or reduced NET clearance, along with alterations of molecules involved in NETosis pathway, in humans and animals with lupus. The extruded nuclear antigens released by NET are a source of autoantigens, which can contribute to the breakdown of self-tolerance in lupus. Excessive NET can also promote the production of pro-inflammatory cytokine interferon-α, elicit direct cytotoxic effect on various renal cells, and cause capillary necrosis and podocyte loss. Additionally, NET can induce endothelial-to-mesenchymal transdifferentiation, which can promote activated myofibroblasts leading to extracellular matrix production. Thus, aberrant NETosis can play diverse roles, including autoantibody production, inflammation, and tissue damage, at different stages of lupus pathogenesis. Evidence suggests that treatments currently used in lupus may reduce NETosis, suggesting a potential utility of targeting NETosis to treat lupus. In fact, several approaches are being experimented to therapeutically target pathways of NETosis. Future studies should precisely delineate distinct roles of NETosis at different stages of lupus pathogenesis in humans, which would offer a rational basis for NETosis-targeting treatments in the clinic.https://www.frontiersin.org/articles/10.3389/fimmu.2022.895216/fullNETosisautoantigenautoantibodypathogenesissystemic lupus erythematosusself-tolerance |
| spellingShingle | Meiying Wang Meiying Wang Tatsuya Ishikawa Yupeng Lai Dhiraj Nallapothula Ram Raj Singh Ram Raj Singh Ram Raj Singh Ram Raj Singh Diverse Roles of NETosis in the Pathogenesis of Lupus Frontiers in Immunology NETosis autoantigen autoantibody pathogenesis systemic lupus erythematosus self-tolerance |
| title | Diverse Roles of NETosis in the Pathogenesis of Lupus |
| title_full | Diverse Roles of NETosis in the Pathogenesis of Lupus |
| title_fullStr | Diverse Roles of NETosis in the Pathogenesis of Lupus |
| title_full_unstemmed | Diverse Roles of NETosis in the Pathogenesis of Lupus |
| title_short | Diverse Roles of NETosis in the Pathogenesis of Lupus |
| title_sort | diverse roles of netosis in the pathogenesis of lupus |
| topic | NETosis autoantigen autoantibody pathogenesis systemic lupus erythematosus self-tolerance |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.895216/full |
| work_keys_str_mv | AT meiyingwang diverserolesofnetosisinthepathogenesisoflupus AT meiyingwang diverserolesofnetosisinthepathogenesisoflupus AT tatsuyaishikawa diverserolesofnetosisinthepathogenesisoflupus AT yupenglai diverserolesofnetosisinthepathogenesisoflupus AT dhirajnallapothula diverserolesofnetosisinthepathogenesisoflupus AT ramrajsingh diverserolesofnetosisinthepathogenesisoflupus AT ramrajsingh diverserolesofnetosisinthepathogenesisoflupus AT ramrajsingh diverserolesofnetosisinthepathogenesisoflupus AT ramrajsingh diverserolesofnetosisinthepathogenesisoflupus |