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Differential isoform expression of Allergin‐1 during acute and chronic inflammation

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 thera...

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Autores principales: Geerdink, Ruben J., Pascoal Ramos, Maria Inês, van den Hoogen, Luuk L., Radstake, Timothy R. D. J., Shibayama, Shiro, Shibuya, Akira, Bont, Louis, Meyaard, Linde
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9695092/
https://www.ncbi.nlm.nih.gov/pubmed/36444625
http://dx.doi.org/10.1002/iid3.739
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author Geerdink, Ruben J.
Pascoal Ramos, Maria Inês
van den Hoogen, Luuk L.
Radstake, Timothy R. D. J.
Shibayama, Shiro
Shibuya, Akira
Bont, Louis
Meyaard, Linde
author_facet Geerdink, Ruben J.
Pascoal Ramos, Maria Inês
van den Hoogen, Luuk L.
Radstake, Timothy R. D. J.
Shibayama, Shiro
Shibuya, Akira
Bont, Louis
Meyaard, Linde
author_sort Geerdink, Ruben J.
collection PubMed
description 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.
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spelling pubmed-96950922022-11-28 Differential isoform expression of Allergin‐1 during acute and chronic inflammation Geerdink, Ruben J. Pascoal Ramos, Maria Inês van den Hoogen, Luuk L. Radstake, Timothy R. D. J. Shibayama, Shiro Shibuya, Akira Bont, Louis Meyaard, Linde Immun Inflamm Dis Short Reports 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. John Wiley and Sons Inc. 2022-11-25 /pmc/articles/PMC9695092/ /pubmed/36444625 http://dx.doi.org/10.1002/iid3.739 Text en © 2022 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Short Reports
Geerdink, Ruben J.
Pascoal Ramos, Maria Inês
van den Hoogen, Luuk L.
Radstake, Timothy R. D. J.
Shibayama, Shiro
Shibuya, Akira
Bont, Louis
Meyaard, Linde
Differential isoform expression of Allergin‐1 during acute and chronic inflammation
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 Short Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9695092/
https://www.ncbi.nlm.nih.gov/pubmed/36444625
http://dx.doi.org/10.1002/iid3.739
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