Background: Eosinophils have numerous roles in type 2 inflammation depending on their activation states in the blood and airway or after encounter with inflammatory mediators. Airway epithelial cells have a sentinel role in the lung and, by instructing eosinophils, likely have a foundational role in asthma pathogenesis. Summary: In this review, we discuss various topics related to eosinophil-epithelial cell interactions in asthma, including the influence of eosinophils and eosinophil products, e.g., granule proteins, on epithelial cell function, expression, secretion, and plasticity; the effects of epithelial released factors, including oxylipins, cytokines, and other mediators on eosinophils, e.g., on their activation, expression, and survival; possible mechanisms of eosinophil-epithelial cell adhesion; and the role of intra-epithelial eosinophils in asthma. Key Messages: We suggest that eosinophils and their products can have both injurious and beneficial effects on airway epithelial cells in asthma and that there are bidirectional interactions and signaling between eosinophils and airway epithelial cells in asthma.

1.
Fahy
JV
,
Jackson
ND
,
Sajuthi
SP
,
Pruesse
E
,
Moore
CM
,
Everman
JL
, et al
.
Asthma severity and corticosteroid response depend on variable type 1 and type 2 inflammation in the airway
.
medRxiv
. [cited 2024 Apr 6]. Available from: https://www.medrxiv.org/content/10.1101/2023.10.05.23296609v1
2.
Fahy
JV
.
Type 2 inflammation in asthma: present in most, absent in many
.
Nat Rev Immunol
.
2015
;
15
(
1
):
57
65
.
3.
Venge
P
.
The eosinophil and airway remodelling in asthma
.
Clin Respir J
.
2010
;
4
(
Suppl 1
):
15
9
.
4.
Siddiqui
S
,
Bachert
C
,
Bjermer
L
,
Buchheit
KM
,
Castro
M
,
Qin
Y
, et al
.
Eosinophils and tissue remodeling: relevance to airway disease
.
J Allergy Clin Immunol
.
2023
;
152
(
4
):
841
57
.
5.
McBrien
CN
,
Menzies-Gow
A
.
The biology of eosinophils and their role in asthma
.
Front Med
.
2017
;
4
:
93
.
6.
Johansson
MW
.
Activation states of blood eosinophils in asthma
.
Clin Exp Allergy
.
2014
;
44
(
4
):
482
98
.
7.
Johansson
MW
.
Eosinophil activation status in separate compartments and association with asthma
.
Front Med
.
2017
;
4
:
75
.
8.
Gigon
L
,
Fettrelet
T
,
Yousefi
S
,
Simon
D
,
Simon
HU
.
Eosinophils from A to Z
.
Allergy
.
2023
;
78
(
7
):
1810
46
.
9.
Jesenak
M
,
Diamant
Z
,
Simon
D
,
Tufvesson
E
,
Seys
SF
,
Mukherjee
M
, et al
.
Eosinophils-from cradle to grave: an EAACI task force paper on new molecular insights and clinical functions of eosinophils and the clinical effects of targeted eosinophil depletion
.
Allergy
.
2023
;
78
(
12
):
3077
102
.
10.
Gurtner
A
,
Borrelli
C
,
Gonzalez-Perez
I
,
Bach
K
,
Acar
IE
,
Núñez
NG
, et al
.
Active eosinophils regulate host defence and immune responses in colitis
.
Nature
.
2023
;
615
(
7950
):
151
7
.
11.
Johansson
MW
.
Not all the same: subtypes of mouse intestinal eosinophils in health and disease models
.
J Leukoc Biol
.
2022
;
111
(
5
):
939
41
.
12.
Larsen
LD
,
Dockstader
K
,
Olbrich
CL
,
Cartwright
IM
,
Spencer
LA
.
Modulation of surface CD11c expression tracks plasticity in murine intestinal tissue eosinophils
.
J Leukoc Biol
.
2022
;
111
(
5
):
943
52
.
13.
Marichal
T
,
Mesnil
C
,
Bureau
F
.
Homeostatic eosinophils: characteristics and functions
.
Front Med
.
2017
;
4
:
101
.
14.
Holgate
ST
.
The sentinel role of the airway epithelium in asthma pathogenesis
.
Immunol Rev
.
2011
;
242
(
1
):
205
19
.
15.
Brasier
AR
.
Innate immunity, epithelial plasticity, and remodeling in asthma
.
Adv Exp Med Biol
.
2023
;
1426
:
265
85
.
16.
Frey
A
,
Lunding
LP
,
Ehlers
JC
,
Weckmann
M
,
Zissler
UM
,
Wegmann
M
.
More than just a barrier: the immune functions of the airway epithelium in asthma pathogenesis
.
Front Immunol
.
2020
;
11
:
761
.
17.
Heijink
IH
,
Kuchibhotla
VNS
,
Roffel
MP
,
Maes
T
,
Knight
DA
,
Sayers
I
, et al
.
Epithelial cell dysfunction, a major driver of asthma development
.
Allergy
.
2020
;
75
(
8
):
1902
17
.
18.
Hellings
PW
,
Steelant
B
.
Epithelial barriers in allergy and asthma
.
J Allergy Clin Immunol
.
2020
;
145
(
6
):
1499
509
.
19.
Raby
KL
,
Michaeloudes
C
,
Tonkin
J
,
Chung
KF
,
Bhavsar
PK
.
Mechanisms of airway epithelial injury and abnormal repair in asthma and COPD
.
Front Immunol
.
2023
;
14
:
1201658
.
20.
Bonser
LR
,
Koh
KD
,
Johansson
K
,
Choksi
SP
,
Cheng
D
,
Liu
L
, et al
.
Flow-cytometric analysis and purification of airway epithelial-cell subsets
.
Am J Respir Cell Mol Biol
.
2021
;
64
(
3
):
308
17
.
21.
Calvén
J
,
Ax
E
,
Rådinger
M
.
The airway epithelium-a central player in asthma pathogenesis
.
Int J Mol Sci
.
2020
;
21
(
23
):
8907
.
22.
Frey
A
,
Lunding
LP
,
Wegmann
M
.
The dual role of the airway epithelium in asthma: active barrier and regulator of inflammation
.
Cells
.
2023
;
12
(
18
):
2208
.
23.
Hammad
H
,
Lambrecht
BN
.
Barrier epithelial cells and the control of type 2 immunity
.
Immunity
.
2015
;
43
(
1
):
29
40
.
24.
Hammad
H
,
Lambrecht
BN
.
The basic immunology of asthma
.
Cell
.
2021
;
184
(
6
):
1469
85
.
25.
Yasukawa
A
,
Hosoki
K
,
Toda
M
,
Miyake
Y
,
Matsushima
Y
,
Matsumoto
T
, et al
.
Eosinophils promote epithelial to mesenchymal transition of bronchial epithelial cells
.
PLoS One
.
2013
;
8
(
5
):
e64281
.
26.
Wilkerson
EM
,
Johansson
MW
,
Hebert
AS
,
Westphall
MS
,
Mathur
SK
,
Jarjour
NN
, et al
.
The peripheral blood eosinophil proteome
.
J Proteome Res
.
2016
;
15
(
5
):
1524
33
.
27.
Shen
ZJ
,
Hu
J
,
Esnault
S
,
Dozmorov
I
,
Malter
JS
.
RNA Seq profiling reveals a novel expression pattern of TGF-β target genes in human blood eosinophils
.
Immunol Lett
.
2015
;
167
(
1
):
1
10
.
28.
Kainuma
K
,
Kobayashi
T
,
D’Alessandro-Gabazza
CN
,
Toda
M
,
Yasuma
T
,
Nishihama
K
, et al
.
β2 adrenergic agonist suppresses eosinophil-induced epithelial-to-mesenchymal transition of bronchial epithelial cells
.
Respir Res
.
2017
;
18
(
1
):
79
.
29.
Hara
K
,
Hasegawa
T
,
Ooi
H
,
Koya
T
,
Tanabe
Y
,
Tsukada
H
, et al
.
Inhibitory role of eosinophils on cell surface plasmin generation by bronchial epithelial cells: inhibitory effects of transforming growth factor beta
.
Lung
.
2001
;
179
(
1
):
9
20
.
30.
Wong
CK
,
Wang
CB
,
Li
MLY
,
Ip
WK
,
Tian
YP
,
Lam
CWK
.
Induction of adhesion molecules upon the interaction between eosinophils and bronchial epithelial cells: involvement of p38 MAPK and NF-kappaB
.
Int Immunopharmacol
.
2006
;
6
(
12
):
1859
71
.
31.
Wong
CK
,
Hu
S
,
Leung
KML
,
Dong
J
,
He
L
,
Chu
YJ
, et al
.
NOD-like receptors mediated activation of eosinophils interacting with bronchial epithelial cells: a link between innate immunity and allergic asthma
.
Cell Mol Immunol
.
2013
;
10
(
4
):
317
29
.
32.
Qiu
HN
,
Wong
CK
,
Dong
J
,
Lam
CWK
,
Cai
Z
.
Effect of tumor necrosis factor family member LIGHT (TNFSF14) on the activation of basophils and eosinophils interacting with bronchial epithelial cells
.
Mediators Inflamm
.
2014
;
2014
:
136463
.
33.
Jiao
D
,
Wong
CK
,
Tsang
MSM
,
Chu
IMT
,
Liu
D
,
Zhu
J
, et al
.
Activation of eosinophils interacting with bronchial epithelial cells by antimicrobial peptide LL-37: implications in allergic asthma
.
Sci Rep
.
2017
;
7
(
1
):
1848
.
34.
Godding
V
,
Stark
JM
,
Sedgwick
JB
,
Busse
WW
.
Adhesion of activated eosinophils to respiratory epithelial cells is enhanced by tumor necrosis factor-alpha and interleukin-1 beta
.
Am J Respir Cell Mol Biol
.
1995
;
13
(
5
):
555
62
.
35.
Sun
X
,
Hou
T
,
Cheung
E
,
Iu
TNT
,
Tam
VWH
,
Chu
IMT
, et al
.
Anti-inflammatory mechanisms of the novel cytokine interleukin-38 in allergic asthma
.
Cell Mol Immunol
.
2020
;
17
(
6
):
631
46
.
36.
Sato
M
,
Takizawa
H
,
Kohyama
T
,
Ohtoshi
T
,
Takafuji
S
,
Kawasaki
S
, et al
.
Eosinophil adhesion to human bronchial epithelial cells: regulation by cytokines
.
Int Arch Allergy Immunol
.
1997
;
113
(
1–3
):
203
5
.
37.
Sanmugalingham
D
,
De Vries
E
,
Gauntlett
R
,
Symon
FA
,
Bradding
P
,
Wardlaw
AJ
.
Interleukin-5 enhances eosinophil adhesion to bronchial epithelial cells
.
Clin Exp Allergy
.
2000
;
30
(
2
):
255
63
.
38.
Suzukawa
M
,
Koketsu
R
,
Iikura
M
,
Nakae
S
,
Matsumoto
K
,
Nagase
H
, et al
.
Interleukin-33 enhances adhesion, CD11b expression and survival in human eosinophils
.
Lab Invest
.
2008
;
88
(
11
):
1245
53
.
39.
Angulo
EL
,
McKernan
EM
,
Fichtinger
PS
,
Mathur
SK
.
Comparison of IL-33 and IL-5 family mediated activation of human eosinophils
.
PLoS One
.
2019
;
14
(
9
):
e0217807
.
40.
Tsang
MSM
,
Sun
X
,
Wong
CK
.
The role of new IL-1 family members (IL-36 and IL-38) in atopic dermatitis, allergic asthma, and allergic rhinitis
.
Curr Allergy Asthma Rep
.
2020
;
20
(
8
):
40
.
41.
Barthel
SR
,
Jarjour
NN
,
Mosher
DF
,
Johansson
MW
.
Dissection of the hyperadhesive phenotype of airway eosinophils in asthma
.
Am J Respir Cell Mol Biol
.
2006
;
35
(
3
):
378
86
.
42.
Johansson
MW
,
Kelly
EAB
,
Busse
WW
,
Jarjour
NN
,
Mosher
DF
.
Up-regulation and activation of eosinophil integrins in blood and airway after segmental lung antigen challenge
.
J Immunol
.
2008
;
180
(
11
):
7622
35
.
43.
Johansson
MW
,
Mosher
DF
.
Integrin activation states and eosinophil recruitment in asthma
.
Front Pharmacol
.
2013
;
4
:
33
.
44.
Johansson
MW
,
Gunderson
KA
,
Kelly
EA
,
Denlinger
LC
,
Jarjour
NN
,
Mosher
DF
.
Anti-IL-5 attenuates activation and surface density of β(2) -integrins on circulating eosinophils after segmental antigen challenge
.
Clin Exp Allergy
.
2013
;
43
(
3
):
292
303
.
45.
Kato
Y
,
Fujisawa
T
,
Shibano
M
,
Saito
T
,
Gatto
W
,
Kamiya
H
, et al
.
Airway epithelial cells promote transmigration of eosinophils in a new three-dimensional chemotaxis model
.
Clin Exp Allergy
.
2002
;
32
(
6
):
889
97
.
46.
Babamale
AO
,
Chen
ST
.
Nod-like receptors: critical intracellular sensors for host protection and cell death in microbial and parasitic infections
.
Int J Mol Sci
.
2021
;
22
(
21
):
11398
.
47.
Esnault
S
,
Hebert
AS
,
Jarjour
NN
,
Coon
JJ
,
Mosher
DF
.
Proteomic and phosphoproteomic changes induced by prolonged activation of human eosinophils with IL-3
.
J Proteome Res
.
2018
;
17
(
6
):
2102
11
.
48.
Mitchell
JM
,
Mabin
JW
,
Muehlbauer
LK
,
Annis
DS
,
Mathur
SK
,
Johansson
MW
, et al
.
Molecular anatomy of eosinophil activation by IL5 and IL33
.
bioRxiv
.
2022
. [cited 2024 Apr 6]. p. 2022.12.21.521419. Available from: https://www.biorxiv.org/content/10.1101/2022.12.21.521419v1
49.
Denlinger
LC
,
Manthei
DM
,
Seibold
MA
,
Ahn
K
,
Bleecker
E
,
Boushey
HA
, et al
.
P2X7-regulated protection from exacerbations and loss of control is independent of asthma maintenance therapy
.
Am J Respir Crit Care Med
.
2013
;
187
(
1
):
28
33
.
50.
Takafuji
S
,
Ohtoshi
T
,
Takizawa
H
,
Tadokoro
K
,
Ito
K
.
Eosinophil degranulation in the presence of bronchial epithelial cells. Effect of cytokines and role of adhesion
.
J Immunol
.
1996
;
156
(
10
):
3980
5
.
51.
Walsh
GM
,
Sexton
DW
,
Blaylock
MG
,
Convery
CM
.
Resting and cytokine-stimulated human small airway epithelial cells recognize and engulf apoptotic eosinophils
.
Blood
.
1999
;
94
(
8
):
2827
35
.
52.
Sexton
DW
,
Blaylock
MG
,
Walsh
GM
.
Human alveolar epithelial cells engulf apoptotic eosinophils by means of integrin- and phosphatidylserine receptor-dependent mechanisms: a process upregulated by dexamethasone
.
J Allergy Clin Immunol
.
2001
;
108
(
6
):
962
9
.
53.
Duchesne
M
,
Okoye
I
,
Lacy
P
.
Epithelial cell alarmin cytokines: frontline mediators of the asthma inflammatory response
.
Front Immunol
.
2022
;
13
:
975914
.
54.
Cherry
WB
,
Yoon
J
,
Bartemes
KR
,
Iijima
K
,
Kita
H
.
A novel IL-1 family cytokine, IL-33, potently activates human eosinophils
.
J Allergy Clin Immunol
.
2008
;
121
(
6
):
1484
90
.
55.
Akdis
M
,
Aab
A
,
Altunbulakli
C
,
Azkur
K
,
Costa
RA
,
Crameri
R
, et al
.
Interleukins (from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-α: receptors, functions, and roles in diseases
.
J Allergy Clin Immunol
.
2016
;
138
(
4
):
984
1010
.
56.
Drake
LY
,
Prakash
YS
.
Contributions of IL-33 in non-hematopoietic lung cells to obstructive lung disease
.
Front Immunol
.
2020
;
11
:
1798
.
57.
Johnston
LK
,
Hsu
CL
,
Krier-Burris
RA
,
Chhiba
KD
,
Chien
KB
,
McKenzie
A
, et al
.
IL-33 precedes IL-5 in regulating eosinophil commitment and is required for eosinophil homeostasis
.
J Immunol
.
2016
;
197
(
9
):
3445
53
.
58.
Johnston
LK
,
Bryce
PJ
.
Understanding interleukin 33 and its roles in eosinophil development
.
Front Med
.
2017
;
4
:
51
.
59.
Johansson
MW
,
Annis
DS
,
Mosher
DF
.
α(M)β(2) integrin-mediated adhesion and motility of IL-5-stimulated eosinophils on periostin
.
Am J Respir Cell Mol Biol
.
2013
;
48
(
4
):
503
10
.
60.
Na
HJ
,
Hudson
SA
,
Bochner
BS
.
IL-33 enhances Siglec-8 mediated apoptosis of human eosinophils
.
Cytokine
.
2012
;
57
(
1
):
169
74
.
61.
Cook
EB
,
Stahl
JL
,
Schwantes
EA
,
Fox
KE
,
Mathur
SK
.
IL-3 and TNFα increase Thymic Stromal Lymphopoietin Receptor (TSLPR) expression on eosinophils and enhance TSLP-stimulated degranulation
.
Clin Mol Allergy
.
2012
;
10
(
1
):
8
.
62.
Soloperto
M
,
Mattoso
VL
,
Fasoli
A
,
Mattoli
S
.
A bronchial epithelial cell-derived factor in asthma that promotes eosinophil activation and survival as GM-CSF
.
Am J Physiol
.
1991
;
260
(
6 Pt 1
):
L530
538
.
63.
Daffern
PJ
,
Jagels
MA
,
Saad
JJ
,
Fischer
W
,
Hugli
TE
.
Upper airway epithelial cells support eosinophil survival in vitro through production of GM-CSF and prostaglandin E2: regulation by glucocorticoids and TNF-alpha
.
Allergy Asthma Proc
.
1999
;
20
(
4
):
243
53
.
64.
Wong
CK
,
Wang
CB
,
Ip
WK
,
Tian
YP
,
Lam
CWK
.
Role of p38 MAPK and NF-kB for chemokine release in coculture of human eosinophils and bronchial epithelial cells
.
Clin Exp Immunol
.
2005
;
139
(
1
):
90
100
.
65.
Larose
MC
,
Archambault
AS
,
Provost
V
,
Laviolette
M
,
Flamand
N
.
Regulation of eosinophil and group 2 innate lymphoid cell trafficking in asthma
.
Front Med
.
2017
;
4
:
136
.
66.
Wang
CB
,
Wong
CK
,
Ip
WK
,
Li
MLY
,
Tian
YP
,
Lam
CWK
.
Induction of IL-6 in co-culture of bronchial epithelial cells and eosinophils is regulated by p38 MAPK and NF-kappaB
.
Allergy
.
2005
;
60
(
11
):
1378
85
.
67.
Peters
MC
,
McGrath
KW
,
Hawkins
GA
,
Hastie
AT
,
Levy
BD
,
Israel
E
, et al
.
Plasma interleukin-6 concentrations, metabolic dysfunction, and asthma severity: a cross-sectional analysis of two cohorts
.
Lancet Respir Med
.
2016
;
4
(
7
):
574
84
.
68.
Al-Shaikhly
T
,
Murphy
RC
,
Parker
A
,
Lai
Y
,
Altman
MC
,
Larmore
M
, et al
.
Location of eosinophils in the airway wall is critical for specific features of airway hyperresponsiveness and T2 inflammation in asthma
.
Eur Respir J
.
2022
;
60
(
2
):
2101865
.
69.
Murphy
RC
,
Lai
Y
,
Liu
M
,
Al-Shaikhly
T
,
Altman
MC
,
Altemeier
WA
, et al
.
Distinct epithelial-innate immune cell transcriptional circuits underlie airway hyperresponsiveness in asthma
.
Am J Respir Crit Care Med
.
2023
;
207
(
12
):
1565
75
.
70.
Jackson
DJ
,
Bacharier
LB
,
Gergen
PJ
,
Gagalis
L
,
Calatroni
A
,
Wellford
S
, et al
.
Mepolizumab for urban children with exacerbation-prone eosinophilic asthma in the USA (MUPPITS-2): a randomised, double-blind, placebo-controlled, parallel-group trial
.
Lancet
.
2022
;
400
(
10351
):
502
11
.
71.
Barretto
KT
,
Brockman-Schneider
RA
,
Kuipers
I
,
Basnet
S
,
Bochkov
YA
,
Altman
MC
, et al
.
Human airway epithelial cells express a functional IL-5 receptor
.
Allergy
.
2020
;
75
(
8
):
2127
30
.
72.
Szczepankiewicz
A
,
Rachel
M
,
Sobkowiak
P
,
Kycler
Z
,
Wojsyk-Banaszak
I
,
Schöneich
N
, et al
.
Neurotrophin serum concentrations and polymorphisms of neurotrophins and their receptors in children with asthma
.
Respir Med
.
2013
;
107
(
1
):
30
6
.
73.
Hahn
C
,
Islamian
AP
,
Renz
H
,
Nockher
WA
.
Airway epithelial cells produce neurotrophins and promote the survival of eosinophils during allergic airway inflammation
.
J Allergy Clin Immunol
.
2006
;
117
(
4
):
787
94
.
74.
Szczepankiewicz
A
,
Rachel
M
,
Sobkowiak
P
,
Kycler
Z
,
Wojsyk-Banaszak
I
,
Schöneich
N
, et al
.
Serum neurotrophin-3 and neurotrophin-4 levels are associated with asthma severity in children
.
Eur Respir J
.
2012
;
39
(
4
):
1035
7
.
75.
Raap
U
,
Deneka
N
,
Bruder
M
,
Kapp
A
,
Wedi
B
.
Differential up-regulation of neurotrophin receptors and functional activity of neurotrophins on peripheral blood eosinophils of patients with allergic rhinitis, atopic dermatitis and nonatopic subjects
.
Clin Exp Allergy
.
2008
;
38
(
9
):
1493
8
.
76.
Drenjančević
I
,
Jukić
I
,
Mihaljević
Z
,
Kibel
,
Drenjančević
I
,
Jukić
I
, et al
.
The metabolites of arachidonic acid in microvascular function
. In:
Microcirculation revisited - from molecules to clinical practice
.
IntechOpen
;
2016
. [cited 2024 Mar 27]. Available from: https://www.intechopen.com/chapters/52272
77.
Wang
B
,
Wu
L
,
Chen
J
,
Dong
L
,
Chen
C
,
Wen
Z
, et al
.
Metabolism pathways of arachidonic acids: mechanisms and potential therapeutic targets
.
Signal Transduct Target Ther
.
2021
;
6
(
1
):
94
30
.
78.
Duvall
MG
,
Bruggemann
TR
,
Levy
BD
.
Bronchoprotective mechanisms for specialized pro-resolving mediators in the resolution of lung inflammation
.
Mol Aspects Med
.
2017
;
58
:
44
56
.
79.
Ferreira
I
,
Falcato
F
,
Bandarra
N
,
Rauter
AP
.
Resolvins, protectins, and maresins: DHA-derived specialized pro-resolving mediators, biosynthetic pathways, synthetic approaches, and their role in inflammation
.
Molecules
.
2022
;
27
(
5
):
1677
.
80.
Gyllfors
P
,
Bochenek
G
,
Overholt
J
,
Drupka
D
,
Kumlin
M
,
Sheller
J
, et al
.
Biochemical and clinical evidence that aspirin-intolerant asthmatic subjects tolerate the cyclooxygenase 2-selective analgetic drug celecoxib
.
J Allergy Clin Immunol
.
2003
;
111
(
5
):
1116
21
.
81.
Aoki
H
,
Hisada
T
,
Ishizuka
T
,
Utsugi
M
,
Kawata
T
,
Shimizu
Y
, et al
.
Resolvin E1 dampens airway inflammation and hyperresponsiveness in a murine model of asthma
.
Biochem Biophys Res Commun
.
2008
;
367
(
2
):
509
15
.
82.
Siddiquee
A
,
Patel
M
,
Rajalingam
S
,
Narke
D
,
Kurade
M
,
Ponnoth
DS
.
Effect of omega-3 fatty acid supplementation on resolvin (RvE1)-mediated suppression of inflammation in a mouse model of asthma
.
Immunopharmacol Immunotoxicol
.
2019
;
41
(
2
):
250
7
.
83.
Insuela
DBR
,
Ferrero
MR
,
Coutinho
DS
,
Martins
MA
,
Carvalho
VF
.
Could arachidonic acid-derived pro-resolving mediators be a new therapeutic strategy for asthma therapy
.
Front Immunol
.
2020
;
11
:
580598
.
84.
Zúñiga-Hernández
J
,
Sambra
V
,
Echeverría
F
,
Videla
LA
,
Valenzuela
R
.
N-3 PUFAs and their specialized pro-resolving lipid mediators on airway inflammatory response: beneficial effects in the prevention and treatment of respiratory diseases
.
Food Funct
.
2022
;
13
(
8
):
4260
72
.
85.
Koshino
T
,
Takano
S
,
Houjo
T
,
Sano
Y
,
Kudo
K
,
Kihara
H
, et al
.
Expression of 5-lipoxygenase and 5-lipoxygenase-activating protein mRNAs in the peripheral blood leukocytes of asthmatics
.
Biochem Biophys Res Commun
.
1998
;
247
(
2
):
510
3
.
86.
Bradding
P
,
Redington
AE
,
Djukanovic
R
,
Conrad
DJ
,
Holgate
ST
.
15-Lipoxygenase immunoreactivity in normal and in asthmatic airways
.
Am J Respir Crit Care Med
.
1995
;
151
(
4
):
1201
4
.
87.
Watkins
DN
,
Peroni
DJ
,
Lenzo
JC
,
Knight
DA
,
Garlepp
MJ
,
Thompson
PJ
.
Expression and localization of COX-2 in human airways and cultured airway epithelial cells
.
Eur Respir J
.
1999
;
13
(
5
):
999
1007
.
88.
Claar
D
,
Hartert
TV
,
Peebles
RS
.
The role of prostaglandins in allergic lung inflammation and asthma
.
Expert Rev Respir Med
.
2015
;
9
(
1
):
55
72
.
89.
Jakiela
B
,
Gielicz
A
,
Plutecka
H
,
Hubalewska
M
,
Mastalerz
L
,
Bochenek
G
, et al
.
Eicosanoid biosynthesis during mucociliary and mucous metaplastic differentiation of bronchial epithelial cells
.
Prostaglandins Other Lipid Mediat
.
2013
;
106
:
116
23
.
90.
Bärnthaler
T
,
Maric
J
,
Platzer
W
,
Konya
V
,
Theiler
A
,
Hasenöhrl
C
, et al
.
The role of PGE2 in alveolar epithelial and lung microvascular endothelial crosstalk
.
Sci Rep
.
2017
;
7
(
1
):
7923
.
91.
Aggarwal
S
,
Moodley
YP
,
Thompson
PJ
,
Misso
NL
.
Prostaglandin E2 and cysteinyl leukotriene concentrations in sputum: association with asthma severity and eosinophilic inflammation
.
Clin Exp Allergy
.
2010
;
40
(
1
):
85
93
.
92.
Sastre
B
,
Fernández-Nieto
M
,
Mollá
R
,
López
E
,
Lahoz
C
,
Sastre
J
, et al
.
Increased prostaglandin E2 levels in the airway of patients with eosinophilic bronchitis
.
Allergy
.
2008
;
63
(
1
):
58
66
.
93.
Sturm
EM
,
Schratl
P
,
Schuligoi
R
,
Konya
V
,
Sturm
GJ
,
Lippe
IT
, et al
.
Prostaglandin E2 inhibits eosinophil trafficking through E-prostanoid 2 receptors
.
J Immunol
.
2008
;
181
(
10
):
7273
83
.
94.
Peinhaupt
M
,
Sturm
EM
,
Heinemann
A
.
Prostaglandins and their receptors in eosinophil function and as therapeutic targets
.
Front Med
.
2017
;
4
:
104
.
95.
Guilbert
M
,
Ferland
C
,
Bossé
M
,
Flamand
N
,
Lavigne
S
,
Laviolette
M
.
5-Oxo-6,8,11,14-eicosatetraenoic acid induces important eosinophil transmigration through basement membrane components: comparison of normal and asthmatic eosinophils
.
Am J Respir Cell Mol Biol
.
1999
;
21
(
1
):
97
104
.
96.
Monneret
G
,
Gravel
S
,
Diamond
M
,
Rokach
J
,
Powell
WS
.
Prostaglandin D2 is a potent chemoattractant for human eosinophils that acts via a novel DP receptor
.
Blood
.
2001
;
98
(
6
):
1942
8
.
97.
Powell
WS
,
Rokach
J
.
The eosinophil chemoattractant 5-oxo-ETE and the OXE receptor
.
Prog Lipid Res
.
2013
;
52
(
4
):
651
65
.
98.
Erlemann
KR
,
Cossette
C
,
Gravel
S
,
Lesimple
A
,
Lee
GJ
,
Saha
G
, et al
.
Airway epithelial cells synthesize the lipid mediator 5-oxo-ETE in response to oxidative stress
.
Free Radic Biol Med
.
2007
;
42
(
5
):
654
64
.
99.
Jawień
J
,
Chłopicki
S
,
Olszanecki
R
,
Lorkowska
B
,
Gryglewski
RJ
.
Eosinophil-epithelial cell interaction augments cysteinyl leukotrienes synthesis
.
J Physiol Pharmacol
.
2002
;
53
(
1
):
127
32
.
100.
Dent
G
,
Rühlmann
E
,
Bodtke
K
,
Magnussen
H
,
Rabe
KF
.
Up-regulation of human eosinophil leukotriene C4 generation through contact with bronchial epithelial cells
.
Inflamm Res
.
2000
;
49
(
5
):
236
9
.
101.
Thompson-Souza
GA
,
Gropillo
I
,
Neves
JS
.
Cysteinyl leukotrienes in eosinophil biology: functional roles and therapeutic perspectives in eosinophilic disorders
.
Front Med
.
2017
;
4
:
106
.
102.
Li
K
,
Zhang
Q
,
Li
L
,
Li
S
,
Yue
Q
,
Li
X
, et al
.
DJ-1 governs airway progenitor cell/eosinophil interactions to promote allergic inflammation
.
J Allergy Clin Immunol
.
2022
;
150
(
5
):
1178
93.e13
.
103.
Johnsson
AK
,
Rönnberg
E
,
Fuchs
D
,
Kolmert
J
,
Säfholm
J
,
Claesson
HE
, et al
.
COX-1 dependent biosynthesis of 15-hydroxyeicosatetraenoic acid in human mast cells
.
Biochim Biophys Acta Mol Cell Biol Lipids
.
2021
;
1866
(
5
):
158886
.
104.
Fahy
JV
,
Dickey
BF
.
Airway mucus function and dysfunction
.
N Engl J Med
.
2010
;
363
(
23
):
2233
47
.
105.
Zhao
J
,
Maskrey
B
,
Balzar
S
,
Chibana
K
,
Mustovich
A
,
Hu
H
, et al
.
Interleukin-13–induced MUC5AC is regulated by 15-lipoxygenase 1 pathway in human bronchial epithelial cells
.
Am J Respir Crit Care Med
.
2009
;
179
(
9
):
782
90
.
106.
Shimizu
S
,
Kouzaki
H
,
Ogawa
T
,
Takezawa
K
,
Tojima
I
,
Shimizu
T
.
Eosinophil-epithelial cell interactions stimulate the production of MUC5AC mucin and profibrotic cytokines involved in airway tissue remodeling
.
Am J Rhinol Allergy
.
2014
;
28
(
2
):
103
9
.
107.
Lachowicz-Scroggins
ME
,
Yuan
S
,
Kerr
SC
,
Dunican
EM
,
Yu
M
,
Carrington
SD
, et al
.
Abnormalities in MUC5AC and MUC5B protein in airway mucus in asthma
.
Am J Respir Crit Care Med
.
2016
;
194
(
10
):
1296
9
.
108.
Kiwamoto
T
,
Katoh
T
,
Evans
CM
,
Janssen
WJ
,
Brummet
ME
,
Hudson
SA
, et al
.
Endogenous airway mucins carry glycans that bind Siglec-F and induce eosinophil apoptosis
.
J Allergy Clin Immunol
.
2015
;
135
(
5
):
1329
40.e9
.
109.
Francisco
D
,
Wang
Y
,
Conway
M
,
Hurbon
AN
,
Dy
ABC
,
Addison
KJ
, et al
.
Surfactant protein-A protects against IL-13–induced inflammation in asthma
.
J Immunol
.
2020
;
204
(
10
):
2829
39
.
110.
Lugogo
N
,
Francisco
D
,
Addison
KJ
,
Manne
A
,
Pederson
W
,
Ingram
JL
, et al
.
Obese asthmatic patients have decreased surfactant protein A levels: mechanisms and implications
.
J Allergy Clin Immunol
.
2018
;
141
(
3
):
918
26.e3
.
111.
Mackay
RMA
,
Grainge
CL
,
Lau
LC
,
Barber
C
,
Clark
HW
,
Howarth
PH
.
Airway surfactant protein D deficiency in adults with severe asthma
.
Chest
.
2016
;
149
(
5
):
1165
72
.
112.
von Bredow
C
,
Hartl
D
,
Schmid
K
,
Schabaz
F
,
Brack
E
,
Reinhardt
D
, et al
.
Surfactant protein D regulates chemotaxis and degranulation of human eosinophils
.
Clin Exp Allergy
.
2006
;
36
(
12
):
1566
74
.
113.
Esnault
S
,
Johansson
MW
,
Kelly
EA
,
Koenderman
L
,
Mosher
DF
,
Jarjour
NN
.
IL-3 up-regulates and activates human eosinophil CD32 and αMβ2 integrin causing degranulation
.
Clin Exp Allergy
.
2017
;
47
(
4
):
488
98
.
114.
Ledford
JG
,
Mukherjee
S
,
Kislan
MM
,
Nugent
JL
,
Hollingsworth
JW
,
Wright
JR
.
Surfactant protein-A suppresses eosinophil-mediated killing of Mycoplasma pneumoniae in allergic lungs
.
PLoS One
.
2012
;
7
(
2
):
e32436
.
115.
Yousefi
S
,
Sharma
SK
,
Stojkov
D
,
Germic
N
,
Aeschlimann
S
,
Ge
MQ
, et al
.
Oxidative damage of SP-D abolishes control of eosinophil extracellular DNA trap formation
.
J Leukoc Biol
.
2018
;
104
(
1
):
205
14
.
116.
Acharya
KR
,
Ackerman
SJ
.
Eosinophil granule proteins: form and function
.
J Biol Chem
.
2014
;
289
(
25
):
17406
15
.
117.
Gleich
GJ
,
Frigas
E
,
Loegering
DA
,
Wassom
DL
,
Steinmuller
D
.
Cytotoxic properties of the eosinophil major basic protein
.
J Immunol
.
1979
;
123
(
6
):
2925
7
.
118.
Frigas
E
,
Loegering
DA
,
Gleich
GJ
.
Cytotoxic effects of the Guinea pig eosinophil major basic protein on tracheal epithelium
.
Lab Invest
.
1980
;
42
(
1
):
35
43
.
119.
Yukawa
T
,
Read
RC
,
Kroegel
C
,
Rutman
A
,
Chung
KF
,
Wilson
R
, et al
.
The effects of activated eosinophils and neutrophils on Guinea pig airway epithelium in vitro
.
Am J Respir Cell Mol Biol
.
1990
;
2
(
4
):
341
53
.
120.
Flavahan
NA
,
Slifman
NR
,
Gleich
GJ
,
Vanhoutte
PM
.
Human eosinophil major basic protein causes hyperreactivity of respiratory smooth muscle. Role of the epithelium
.
Am Rev Respir Dis
.
1988
;
138
(
3
):
685
8
.
121.
Gleich
GJ
,
Flavahan
NA
,
Fujisawa
T
,
Vanhoutte
PM
.
The eosinophil as a mediator of damage to respiratory epithelium: a model for bronchial hyperreactivity
.
J Allergy Clin Immunol
.
1988
;
81
(
5 Pt 1
):
776
81
.
122.
Chihara
J
,
Urayama
O
,
Tsuda
A
,
Kakazu
T
,
Higashimoto
I
,
Yamada
H
.
Eosinophil cationic protein induces insulin-like growth factor I receptor expression on bronchial epithelial cells
.
Int Arch Allergy Immunol
.
1996
;
111
(
Suppl 1
):
43
5
.
123.
Pégorier
S
,
Wagner
LA
,
Gleich
GJ
,
Pretolani
M
.
Eosinophil-derived cationic proteins activate the synthesis of remodeling factors by airway epithelial cells
.
J Immunol
.
2006
;
177
(
7
):
4861
9
.
124.
Mathur
SK
,
Fichtinger
PS
,
Kelly
JT
,
Lee
WM
,
Gern
JE
,
Jarjour
NN
.
Interaction between allergy and innate immunity: model for eosinophil regulation of epithelial cell interferon expression
.
Ann Allergy Asthma Immunol
.
2013
;
111
(
1
):
25
31
.
125.
Contoli
M
,
Message
SD
,
Laza-Stanca
V
,
Edwards
MR
,
Wark
PAB
,
Bartlett
NW
, et al
.
Role of deficient type III interferon-lambda production in asthma exacerbations
.
Nat Med
.
2006
;
12
(
9
):
1023
6
.
126.
Wark
PAB
,
Johnston
SL
,
Bucchieri
F
,
Powell
R
,
Puddicombe
S
,
Laza-Stanca
V
, et al
.
Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus
.
J Exp Med
.
2005
;
201
(
6
):
937
47
.
127.
Tiwary
M
,
Rooney
RJ
,
Liedmann
S
,
LeMessurier
KS
,
Samarasinghe
AE
.
Eosinophil responses at the airway epithelial barrier during the early phase of influenza a virus infection in C57BL/6 Mice
.
Cells
.
2021
;
10
(
3
):
509
.
128.
Zamprogno
P
,
Wüthrich
S
,
Achenbach
S
,
Thoma
G
,
Stucki
JD
,
Hobi
N
, et al
.
Second-generation lung-on-a-chip with an array of stretchable alveoli made with a biological membrane
.
Commun Biol
.
2021
;
4
(
1
):
168
10
.
129.
Huh
D
,
Matthews
BD
,
Mammoto
A
,
Montoya-Zavala
M
,
Hsin
HY
,
Ingber
DE
.
Reconstituting organ-level lung functions on a chip
.
Science
.
2010
;
328
(
5986
):
1662
8
.
130.
Humayun
M
,
Chow
CW
,
Young
EWK
.
Microfluidic lung airway-on-a-chip with arrayable suspended gels for studying epithelial and smooth muscle cell interactions
.
Lab Chip
.
2018
;
18
(
9
):
1298
309
.
131.
Barkal
LJ
,
Procknow
CL
,
Álvarez-García
YR
,
Niu
M
,
Jiménez-Torres
JA
,
Brockman-Schneider
RA
, et al
.
Microbial volatile communication in human organotypic lung models
.
Nat Commun
.
2017
;
8
(
1
):
1770
.
132.
Miller
AJ
,
Dye
BR
,
Ferrer-Torres
D
,
Hill
DR
,
Overeem
AW
,
Shea
LD
, et al
.
Generation of lung organoids from human pluripotent stem cells in vitro
.
Nat Protoc
.
2019
;
14
(
2
):
518
40
.
133.
Tindle
C
,
Fuller
M
,
Fonseca
A
,
Taheri
S
,
Ibeawuchi
SR
,
Beutler
N
, et al
.
Adult stem cell-derived complete lung organoid models emulate lung disease in COVID-19
.
Elife
.
2021
;
10
:
e66417
.
134.
Bosáková
V
,
De Zuani
M
,
Sládková
L
,
Garlíková
Z
,
Jose
SS
,
Zelante
T
, et al
.
Lung organoids: the ultimate tool to dissect pulmonary diseases
.
Front Cell Dev Biol
.
2022
;
10
:
899368
.
135.
Kühl
L
,
Graichen
P
,
von Daacke
N
,
Mende
A
,
Wygrecka
M
,
Potaczek
DP
, et al
.
Human lung organoids: a novel experimental and precision medicine approach
.
Cells
.
2023
;
12
(
16
):
2067
.
You do not currently have access to this content.