Differential isoform expression of Allergin‐1 during acute and chronic inflammation
Abstract Introduction Neutrophils are crucial to antimicrobial defense, but excessive neutrophilic inflammation elicits immune pathology. Currently, no effective treatment exists to curb neutrophil activation. However, neutrophils express a variety of inhibitory receptors which may represent potenti...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-12-01
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| Series: | Immunity, Inflammation and Disease |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/iid3.739 |
| _version_ | 1811323025626234880 |
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| author | Ruben J. Geerdink Maria Inês Pascoal Ramos Luuk L. van denHoogen Timothy R. D. J. Radstake Shiro Shibayama Akira Shibuya Louis Bont Linde Meyaard |
| author_facet | Ruben J. Geerdink Maria Inês Pascoal Ramos Luuk L. van denHoogen Timothy R. D. J. Radstake Shiro Shibayama Akira Shibuya Louis Bont Linde Meyaard |
| author_sort | Ruben J. Geerdink |
| collection | DOAJ |
| description | Abstract Introduction Neutrophils are crucial to antimicrobial defense, but excessive neutrophilic inflammation elicits immune pathology. Currently, no effective treatment exists to curb neutrophil activation. However, neutrophils express a variety of inhibitory receptors which may represent potential therapeutic targets to limit neutrophilic inflammation. Indeed, we previously showed that the inhibitory collagen receptor leukocyte‐associated immunoglobulin‐like receptor 1 (LAIR‐1) regulates neutrophilic airway inflammation and inhibits neutrophil extracellular trap formation. The inhibitory receptor Allergin‐1 is expressed by myeloid cells and B cells. Allergin‐1 suppresses mast cell and basophil activation, but a potential regulatory role on neutrophils remains unexplored. We aimed to demonstrate the regulation of neutrophils by Allergin‐1. Methods We examine Allergin‐1 isoform expression on human neutrophils during homeostatic (healthy donors) and chronic inflammatory (systemic lupus erythematosus patients) conditions in comparison to other circulating leukocytes by flow cytometry. To reveal a potential role for Allergin‐1 in regulating neutrophilic inflammation, we experimentally infect wild‐type (WT) and Allergin‐1‐deficient mice with a respiratory syncytial virus (RSV) and monitor disease severity and examine cellular airway infiltrate. Flow cytometry was used to confirm Allergin‐1 expression by airway‐infiltrated neutrophils in RSV infection‐induced bronchiolitis patients. Results Only the short 1 (S1) isoform, but not the long (L) or S2 isoform could be detected on blood leukocytes, with the exception of nonclassical monocytes, which exclusively express the S2 isoform. Allergin‐1 expression levels did not vary significantly between healthy individuals and patients with the systemic inflammatory disease on any interrogated cell type. Airway‐infiltrated neutrophils of pediatric RSV bronchiolitis patients were found to express Allergin‐1S1. However, Allergin‐1‐deficient mice experimentally infected with RSV did not show exacerbated disease or increased neutrophil airway infiltration compared to WT littermates. Conclusion Allergin‐1 isoform expression is unaffected by chronic inflammatory conditions. In stark contrast to fellow inhibitory receptor LAIR‐1, Allergin‐1 does not regulate neutrophilic inflammation in a mouse model of RSV bronchiolitis. |
| first_indexed | 2024-04-13T13:46:43Z |
| format | Article |
| id | doaj.art-6f3d235b6dc740b48e9a6800237a410d |
| institution | Directory Open Access Journal |
| issn | 2050-4527 |
| language | English |
| last_indexed | 2024-04-13T13:46:43Z |
| publishDate | 2022-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Immunity, Inflammation and Disease |
| spelling | doaj.art-6f3d235b6dc740b48e9a6800237a410d2022-12-22T02:44:28ZengWileyImmunity, Inflammation and Disease2050-45272022-12-011012n/an/a10.1002/iid3.739Differential isoform expression of Allergin‐1 during acute and chronic inflammationRuben J. Geerdink0Maria Inês Pascoal Ramos1Luuk L. van denHoogen2Timothy R. D. J. Radstake3Shiro Shibayama4Akira Shibuya5Louis Bont6Linde Meyaard7Center for Translational Immunology, University Medical Centre Utrecht Utrecht University Utrecht The NetherlandsCenter for Translational Immunology, University Medical Centre Utrecht Utrecht University Utrecht The NetherlandsDepartment of Rheumatology and Clinical Immunology University Medical Centre Utrecht Utrecht The NetherlandsCenter for Translational Immunology, University Medical Centre Utrecht Utrecht University Utrecht The NetherlandsResearch Centre of Immunology, Tsukuba Institute ONO Pharmaceutical Co., Ltd. Tsukuba Ibaraki JapanDepartment of Immunology, Faculty of Medicine University of Tsukuba Tsukuba Ibaraki JapanCenter for Translational Immunology, University Medical Centre Utrecht Utrecht University Utrecht The NetherlandsCenter for Translational Immunology, University Medical Centre Utrecht Utrecht University Utrecht The NetherlandsAbstract Introduction Neutrophils are crucial to antimicrobial defense, but excessive neutrophilic inflammation elicits immune pathology. Currently, no effective treatment exists to curb neutrophil activation. However, neutrophils express a variety of inhibitory receptors which may represent potential therapeutic targets to limit neutrophilic inflammation. Indeed, we previously showed that the inhibitory collagen receptor leukocyte‐associated immunoglobulin‐like receptor 1 (LAIR‐1) regulates neutrophilic airway inflammation and inhibits neutrophil extracellular trap formation. The inhibitory receptor Allergin‐1 is expressed by myeloid cells and B cells. Allergin‐1 suppresses mast cell and basophil activation, but a potential regulatory role on neutrophils remains unexplored. We aimed to demonstrate the regulation of neutrophils by Allergin‐1. Methods We examine Allergin‐1 isoform expression on human neutrophils during homeostatic (healthy donors) and chronic inflammatory (systemic lupus erythematosus patients) conditions in comparison to other circulating leukocytes by flow cytometry. To reveal a potential role for Allergin‐1 in regulating neutrophilic inflammation, we experimentally infect wild‐type (WT) and Allergin‐1‐deficient mice with a respiratory syncytial virus (RSV) and monitor disease severity and examine cellular airway infiltrate. Flow cytometry was used to confirm Allergin‐1 expression by airway‐infiltrated neutrophils in RSV infection‐induced bronchiolitis patients. Results Only the short 1 (S1) isoform, but not the long (L) or S2 isoform could be detected on blood leukocytes, with the exception of nonclassical monocytes, which exclusively express the S2 isoform. Allergin‐1 expression levels did not vary significantly between healthy individuals and patients with the systemic inflammatory disease on any interrogated cell type. Airway‐infiltrated neutrophils of pediatric RSV bronchiolitis patients were found to express Allergin‐1S1. However, Allergin‐1‐deficient mice experimentally infected with RSV did not show exacerbated disease or increased neutrophil airway infiltration compared to WT littermates. Conclusion Allergin‐1 isoform expression is unaffected by chronic inflammatory conditions. In stark contrast to fellow inhibitory receptor LAIR‐1, Allergin‐1 does not regulate neutrophilic inflammation in a mouse model of RSV bronchiolitis.https://doi.org/10.1002/iid3.739inhibitory receptorneutrophilsnonclassical monocytesrespiratory syncytial virussystemic lupus erythematosus |
| spellingShingle | Ruben J. Geerdink Maria Inês Pascoal Ramos Luuk L. van denHoogen Timothy R. D. J. Radstake Shiro Shibayama Akira Shibuya Louis Bont Linde Meyaard Differential isoform expression of Allergin‐1 during acute and chronic inflammation Immunity, Inflammation and Disease inhibitory receptor neutrophils nonclassical monocytes respiratory syncytial virus systemic lupus erythematosus |
| title | Differential isoform expression of Allergin‐1 during acute and chronic inflammation |
| title_full | Differential isoform expression of Allergin‐1 during acute and chronic inflammation |
| title_fullStr | Differential isoform expression of Allergin‐1 during acute and chronic inflammation |
| title_full_unstemmed | Differential isoform expression of Allergin‐1 during acute and chronic inflammation |
| title_short | Differential isoform expression of Allergin‐1 during acute and chronic inflammation |
| title_sort | differential isoform expression of allergin 1 during acute and chronic inflammation |
| topic | inhibitory receptor neutrophils nonclassical monocytes respiratory syncytial virus systemic lupus erythematosus |
| url | https://doi.org/10.1002/iid3.739 |
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