Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1784837970440749056 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9695092 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT geerdinkrubenj differentialisoformexpressionofallergin1duringacuteandchronicinflammation AT pascoalramosmariaines differentialisoformexpressionofallergin1duringacuteandchronicinflammation AT vandenhoogenluukl differentialisoformexpressionofallergin1duringacuteandchronicinflammation AT radstaketimothyrdj differentialisoformexpressionofallergin1duringacuteandchronicinflammation AT shibayamashiro differentialisoformexpressionofallergin1duringacuteandchronicinflammation AT shibuyaakira differentialisoformexpressionofallergin1duringacuteandchronicinflammation AT bontlouis differentialisoformexpressionofallergin1duringacuteandchronicinflammation AT meyaardlinde differentialisoformexpressionofallergin1duringacuteandchronicinflammation |