Location of eosinophils in the airway wall is critical for specific features of airway hyperresponsiveness and T2 inflammation in asthma
Copyright ©The authors 2022. For reproduction rights and permissions contact permissionsersnet.org..
BACKGROUND: Eosinophils are implicated as effector cells in asthma, but the functional implications of the precise location of eosinophils in the airway wall is poorly understood. We aimed to quantify eosinophils in the different compartments of the airway wall and associate these findings with clinical features of asthma and markers of airway inflammation.
METHODS: In this cross-sectional study, we utilised design-based stereology to accurately partition the numerical density of eosinophils in both the epithelial compartment and the subepithelial space (airway wall area below the basal lamina including the submucosa) in individuals with and without asthma and related these findings to airway hyperresponsiveness (AHR) and features of airway inflammation.
RESULTS: Intraepithelial eosinophils were linked to the presence of asthma and endogenous AHR, the type that is most specific for asthma. In contrast, both intraepithelial and subepithelial eosinophils were associated with type 2 (T2) inflammation, with the strongest association between IL5 expression and intraepithelial eosinophils. Eosinophil infiltration of the airway wall was linked to a specific mast cell phenotype that has been described in asthma. We found that interleukin (IL)-33 and IL-5 additively increased cysteinyl leukotriene (CysLT) production by eosinophils and that the CysLT LTC4 along with IL-33 increased IL13 expression in mast cells and altered their protease profile.
CONCLUSIONS: We conclude that intraepithelial eosinophils are associated with endogenous AHR and T2 inflammation and may interact with intraepithelial mast cells via CysLTs to regulate airway inflammation.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:60 |
|---|---|
| Enthalten in: |
The European respiratory journal - 60(2022), 2 vom: 13. Aug. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Al-Shaikhly, Taha [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| Anmerkungen: |
Date Completed 08.08.2022 Date Revised 05.08.2023 published: Electronic-Print Citation Status MEDLINE |
|---|
| doi: |
10.1183/13993003.01865-2021 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM335622593 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM335622593 | ||
| 003 | DE-627 | ||
| 005 | 20231225230253.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1183/13993003.01865-2021 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1118.xml |
| 035 | |a (DE-627)NLM335622593 | ||
| 035 | |a (NLM)35027395 | ||
| 035 | |a (PII)2101865 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Al-Shaikhly, Taha |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Location of eosinophils in the airway wall is critical for specific features of airway hyperresponsiveness and T2 inflammation in asthma |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 08.08.2022 | ||
| 500 | |a Date Revised 05.08.2023 | ||
| 500 | |a published: Electronic-Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright ©The authors 2022. For reproduction rights and permissions contact permissionsersnet.org. | ||
| 520 | |a BACKGROUND: Eosinophils are implicated as effector cells in asthma, but the functional implications of the precise location of eosinophils in the airway wall is poorly understood. We aimed to quantify eosinophils in the different compartments of the airway wall and associate these findings with clinical features of asthma and markers of airway inflammation | ||
| 520 | |a METHODS: In this cross-sectional study, we utilised design-based stereology to accurately partition the numerical density of eosinophils in both the epithelial compartment and the subepithelial space (airway wall area below the basal lamina including the submucosa) in individuals with and without asthma and related these findings to airway hyperresponsiveness (AHR) and features of airway inflammation | ||
| 520 | |a RESULTS: Intraepithelial eosinophils were linked to the presence of asthma and endogenous AHR, the type that is most specific for asthma. In contrast, both intraepithelial and subepithelial eosinophils were associated with type 2 (T2) inflammation, with the strongest association between IL5 expression and intraepithelial eosinophils. Eosinophil infiltration of the airway wall was linked to a specific mast cell phenotype that has been described in asthma. We found that interleukin (IL)-33 and IL-5 additively increased cysteinyl leukotriene (CysLT) production by eosinophils and that the CysLT LTC4 along with IL-33 increased IL13 expression in mast cells and altered their protease profile | ||
| 520 | |a CONCLUSIONS: We conclude that intraepithelial eosinophils are associated with endogenous AHR and T2 inflammation and may interact with intraepithelial mast cells via CysLTs to regulate airway inflammation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 700 | 1 | |a Murphy, Ryan C |e verfasserin |4 aut | |
| 700 | 1 | |a Parker, Andrew |e verfasserin |4 aut | |
| 700 | 1 | |a Lai, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Altman, Matthew C |e verfasserin |4 aut | |
| 700 | 1 | |a Larmore, Megan |e verfasserin |4 aut | |
| 700 | 1 | |a Altemeier, William A |e verfasserin |4 aut | |
| 700 | 1 | |a Frevert, Charles W |e verfasserin |4 aut | |
| 700 | 1 | |a Debley, Jason S |e verfasserin |4 aut | |
| 700 | 1 | |a Piliponsky, Adrian M |e verfasserin |4 aut | |
| 700 | 1 | |a Ziegler, Steven F |e verfasserin |4 aut | |
| 700 | 1 | |a Peters, Michael C |e verfasserin |4 aut | |
| 700 | 1 | |a Hallstrand, Teal S |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The European respiratory journal |d 1989 |g 60(2022), 2 vom: 13. Aug. |w (DE-627)NLM012664782 |x 0903-1936 |7 nnns |
| 773 | 1 | 8 | |g volume:60 |g year:2022 |g number:2 |g day:13 |g month:08 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1183/13993003.01865-2021 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 60 |j 2022 |e 2 |b 13 |c 08 | ||