IgE Immune Complexes Mitigate Eosinophilic Immune Responses through NLRC4 Inflammasome
Immune complexes (ICs) skew immune responses toward either a pro- or anti-inflammatory direction based on the type of stimulation. Immunoglobulin E (IgE) is associated with Th2 immune responses and known to activate innate immune cells. However, roles of antigen (Ag)-specific-IgE ICs in regulating h...
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| Format: | Article |
| Language: | English |
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Wiley
2023-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2023/3224708 |
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| author | Ece Oylumlu Goksu Uzel Lubeyne Durmus Ceren Ciraci |
| author_facet | Ece Oylumlu Goksu Uzel Lubeyne Durmus Ceren Ciraci |
| author_sort | Ece Oylumlu |
| collection | DOAJ |
| description | Immune complexes (ICs) skew immune responses toward either a pro- or anti-inflammatory direction based on the type of stimulation. Immunoglobulin E (IgE) is associated with Th2 immune responses and known to activate innate immune cells. However, roles of antigen (Ag)-specific-IgE ICs in regulating human eosinophil responses remain elusive; therefore, this study builts upon the mechanism of which ovalbumin (Ova)-IgE ICs affects eosinophilic responses utilizing human EoL-1 cell line as a model. Eosinophils are granulocytes functioning through pattern recognition receptors (PRRs) and destructive granule contents in allergic inflammation and parasitic infections. One of the PRRs that eosinophils express is NLRC4, a member of the CARD domain containing nucleotide-binding oligomerization (NOD)-like receptor (NLR) family. Upon recognition of its specific ligand flagellin, NLRC4 inflammasome is formed and leads to the release of interleukin-1β (IL-1β). We exhibited that Ova-IgE ICs induced the NLRC4-inflammasome components, including NLRC4, caspase-1, intracellular IL-1β, and secretion of IL-1β, as well as the granule contents MMP9, TIMP1, and TIMP2 proteins via TLR2 signaling; these responses were suppressed, when NLRC4 inflammasome got actived in the presence of ICs. Furthermore, Ova-IgE ICs induced mRNA expressions of MMP9, TIMP2, and ECP and protein expressions of MMP9 and TIMP2 in EoL-1 through FcɛRII. Interestingly, TLR2 ligand and Ova-IgE ICs costimulation elevated the number of CD63+ cells, a degranulation marker, as compared to the native IgE. Collectively, our findings provide a mechanism for the impacts of Ova-IgE ICs on eosinophilic responses via NLRC4-inflammasome and may help understand eosinophil-associated diseases, including chronic eosinophilic pneumonia, eosinophilic esophagitis, eosinophilic granulomatosis, parasitic infections, allergy, and asthma. |
| format | Article |
| id | doaj-art-0e05367490bc4b5fb617d3578fc795a2 |
| institution | DOAJ |
| issn | 1466-1861 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-0e05367490bc4b5fb617d3578fc795a22025-08-20T03:17:19ZengWileyMediators of Inflammation1466-18612023-01-01202310.1155/2023/3224708IgE Immune Complexes Mitigate Eosinophilic Immune Responses through NLRC4 InflammasomeEce Oylumlu0Goksu Uzel1Lubeyne Durmus2Ceren Ciraci3Molecular Biology and Genetics DepartmentMolecular Biology and Genetics DepartmentMolecular Biology and Genetics DepartmentMolecular Biology and Genetics DepartmentImmune complexes (ICs) skew immune responses toward either a pro- or anti-inflammatory direction based on the type of stimulation. Immunoglobulin E (IgE) is associated with Th2 immune responses and known to activate innate immune cells. However, roles of antigen (Ag)-specific-IgE ICs in regulating human eosinophil responses remain elusive; therefore, this study builts upon the mechanism of which ovalbumin (Ova)-IgE ICs affects eosinophilic responses utilizing human EoL-1 cell line as a model. Eosinophils are granulocytes functioning through pattern recognition receptors (PRRs) and destructive granule contents in allergic inflammation and parasitic infections. One of the PRRs that eosinophils express is NLRC4, a member of the CARD domain containing nucleotide-binding oligomerization (NOD)-like receptor (NLR) family. Upon recognition of its specific ligand flagellin, NLRC4 inflammasome is formed and leads to the release of interleukin-1β (IL-1β). We exhibited that Ova-IgE ICs induced the NLRC4-inflammasome components, including NLRC4, caspase-1, intracellular IL-1β, and secretion of IL-1β, as well as the granule contents MMP9, TIMP1, and TIMP2 proteins via TLR2 signaling; these responses were suppressed, when NLRC4 inflammasome got actived in the presence of ICs. Furthermore, Ova-IgE ICs induced mRNA expressions of MMP9, TIMP2, and ECP and protein expressions of MMP9 and TIMP2 in EoL-1 through FcɛRII. Interestingly, TLR2 ligand and Ova-IgE ICs costimulation elevated the number of CD63+ cells, a degranulation marker, as compared to the native IgE. Collectively, our findings provide a mechanism for the impacts of Ova-IgE ICs on eosinophilic responses via NLRC4-inflammasome and may help understand eosinophil-associated diseases, including chronic eosinophilic pneumonia, eosinophilic esophagitis, eosinophilic granulomatosis, parasitic infections, allergy, and asthma.http://dx.doi.org/10.1155/2023/3224708 |
| spellingShingle | Ece Oylumlu Goksu Uzel Lubeyne Durmus Ceren Ciraci IgE Immune Complexes Mitigate Eosinophilic Immune Responses through NLRC4 Inflammasome Mediators of Inflammation |
| title | IgE Immune Complexes Mitigate Eosinophilic Immune Responses through NLRC4 Inflammasome |
| title_full | IgE Immune Complexes Mitigate Eosinophilic Immune Responses through NLRC4 Inflammasome |
| title_fullStr | IgE Immune Complexes Mitigate Eosinophilic Immune Responses through NLRC4 Inflammasome |
| title_full_unstemmed | IgE Immune Complexes Mitigate Eosinophilic Immune Responses through NLRC4 Inflammasome |
| title_short | IgE Immune Complexes Mitigate Eosinophilic Immune Responses through NLRC4 Inflammasome |
| title_sort | ige immune complexes mitigate eosinophilic immune responses through nlrc4 inflammasome |
| url | http://dx.doi.org/10.1155/2023/3224708 |
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