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A substantial neutrophilic inflammation as regular part of severe type 2 chronic rhinosinusitis with nasal polyps - 09/01/21

Doi : 10.1016/j.jaci.2020.08.036 
Tim Delemarre, MSc a, Gabriele Holtappels, BSc a, Natalie De Ruyck, MSc a, Nan Zhang, MD, PhD a, Hans Nauwynck, DVM, PhD b, Claus Bachert, MD, PhD a, c, , Elien Gevaert, PhD a,
a Upper Airways Research Laboratory, Faculty of Medicine, Ghent University, Ghent, Belgium 
b Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Ghent University, Ghent, Belgium 
c Division of Ear, Nose and Throat Diseases, Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden 

Corresponding author: Claus Bachert, MD, PhD, Upper Airways Research Laboratory, Department Head and Skin, Ghent University, UZ Ghent, C. Heymanslaan 10, 9000 Ghent, Belgium.Upper Airways Research LaboratoryDepartment Head and SkinGhent UniversityUZ GhentC. Heymanslaan 10Ghent9000Belgium

Abstract

Background

Chronic rhinosinusitis with nasal polyps (CRSwNP) is generally associated with severe type 2 immune reactions in the white population. However, recent findings suggest an additional role for neutrophils in severe type 2 inflammation.

Objective

This study aimed to characterize the neutrophilic inflammation in CRSwNP and its relation to eosinophilic inflammation in severe type 2 immune reactions.

Methods

The presence and activation of neutrophils and eosinophils was analyzed in CRS without NP and CRSwNP by measuring cell and activation markers via immunohistochemistry, immunofluorescence, Luminex assay, ELISA, UniCAP, fluorescence-activated cell sorting, and PCR. Differential neutrophil migration was assessed via Boyden-chamber assay and neutrophil survival was analyzed via flow cytometry.

Results

Both CRS without NP and CRSwNP displayed variable degrees of eosinophilic and neutrophilic inflammation, with a profound neutrophilic infiltration and activation in type 2 CRSwNP, associated with eosinophil extracellular traps cell death and Charcot-Leyden crystals, but independent of IL-17. Neutrophil extracellular traps cell death in CRSwNP was associated with bacterial colonization, however, neutrophils were less prone to undergo neutrophil extracellular traps cell death in the tissue of patients with severe type 2 CRSwNP. Neutrophils did not show increased migration nor survival in the CRSwNP environment in vitro.

Conclusions

This study demonstrated a severe neutrophilic inflammation associated with severe eosinophilic type 2 inflammatory CRSwNP, the role of which needs further study.

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Key words : CRSsNP, CRSwNP, type 2 inflammation, neutrophils, NETosis, IL-17, Charcot-Leyden crystals

Abbreviations used : CitH3, CLC, CRS, CRSsNP, CRSwNP, EETosis, Gal10, MBP, NETosis


Mappa


 E.G. was supported by a post-doctoral research fellowship from the Fonds Wetenschappelijk Onderzoek (FWO) (FWO/DPO/108). C.B. and E.G. were supported by grants from FWO Flanders (1515516N, EOS GOG2318N), the Interuniversity Attraction Poles Grant P7/30, and Sanofi (A17/TT/1942, A19/TT/0828).
 Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.


© 2020  American Academy of Allergy, Asthma & Immunology. Pubblicato da Elsevier Masson SAS. Tutti i diritti riservati.
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