Abstract
Introduction: CD8+CD25+Foxp3+ regulatory T cells (Tregs) play an important role in human’s immune tolerance. The study was aimed to assess the influence of budesonide nasal spray on CD8+CD25+Foxp3+ Tregs and to evaluate their cellular functions in neutrophilic chronic rhinosinusitis with nasal polyps (CRSwNPs). Methods: Fifteen patients with neutrophilic CRSwNPs were enrolled and received physiological saline or budesonide nasal spray treatment (Saline or Budesonide group) for 3 months. Nasal tissue samples were obtained from normal subjects or those patients and cultured in vitro. CD8+CD25+Foxp3+ Tregs were separated from normal or NP tissues and also cultured in vitro. Then interleukin (IL)-10 and its mRNA were evaluated in the above cell cultures. The cells were applied into NP cultures. Finally, myeloperoxidase (MPO), interferon (IFN)-γ, IL-1β, and tumor necrosis factor (TNF)-α were assessed in the tissue cultures. Results: CD8+CD25+Foxp3+ Tregs decreased in NP tissues. Budesonide administration did not enhance the percentage of these cells in polypoid tissues. IL-10 and its mRNA were increased in the above cell cultures from NPs. However, there were no statistical differences between the two treatments in the IL-10 expression. Additionally, levels of MPO, IFN-γ, IL-1β, and TNF-α were totally elevated in NP tissue cultures and reduced after the administration of CD8+CD25+Foxp3+ Tregs. However, there were no significant differences in concentrations of these mediators between these two groups of the CD8+CD25+Foxp3+ Tregs treatment in vitro. Conclusion: The findings indicate that CD8+CD25+Foxp3+ Tregs might regulate the neutrophilic inflammation, and budesonide nasal spray therapy could not ameliorate the inflammation in neutrophilic CRSwNPs.
References
1.
Payne
SC
, Early
SB
, Huyett
P
, Han
JK
, Borish
L
, Steinke
JW
. Evidence for distinct histologic profile of nasal polyps with and without eosinophilia
. Laryngoscope
. 2011
;121
(10
):2262
–7
. .2.
Soyka
MB
, Wawrzyniak
P
, Eiwegger
T
, Holzmann
D
, Treis
A
, Wanke
K
, Defective epithelial barrier in chronic rhinosinusitis: the regulation of tight junctions by IFN-gamma and IL-4
. J Allergy Clin Immunol
. 2012
;130
(5
):1087
–96.e10
.3.
Fokkens
WJ
, Lund
VJ
, Mullol
J
, Bachert
C
, Alobid
I
, Baroody
F
, European position paper on rhinosinusitis and nasal polyps 2012
. Rhinol Suppl
. 2012
;23
. 3p preceding table of contents:1–298.4.
Jankowski
R
, Bouchoua
F
, Coffinet
L
, Vignaud
JM
. Clinical factors influencing the eosinophil infiltration of nasal polyps
. Rhinology
. 2002
;40
(4
):173
–8
.5.
Zhang
N
, Van Zele
T
, Perez-Novo
C
, Van Bruaene
N
, Holtappels
G
, DeRuyck
N
, Different types of T-effector cells orchestrate mucosal inflammation in chronic sinus disease
. J Allergy Clin Immunol
. 2008
;122
(5
):961
–8
.6.
Hellquist
HB
. Nasal polyps update. Histopathology
. Allergy Asthma Proc
. 1996 Sep–Oct
;17
(5
):237
–42
. .7.
Shin
SH
, Ye
MK
, Kim
JK
, Cho
CH
. Histological characteristics of chronic rhinosinusitis with nasal polyps: recent 10-year experience of a single center in Daegu, Korea
. Am J Rhinol Allergy
. 2014
;28
(2
):95
–8
. .8.
Wing
K
, Sakaguchi
S
. Regulatory T cells exert checks and balances on self tolerance and autoimmunity
. Nat Immunol
. 2010
;11
(1
):7
–13
. .9.
Robb
RJ
, Lineburg
KE
, Kuns
RD
, Wilson
YA
, Raffelt
NC
, Olver
SD
, Identification and expansion of highly suppressive CD8(+)FoxP3(+) regulatory T cells after experimental allogeneic bone marrow transplantation
. Blood
. 2012
;119
(24
):5898
–908
.10.
Peng
LS
, Zhuang
Y
, Shi
Y
, Zhao
YL
, Wang
TT
, Chen
N
, Increased tumor-infiltrating CD8(+)Foxp3(+) T lymphocytes are associated with tumor progression in human gastric cancer
. Cancer Immunol Immunother
. 2012
;61
(11
):2183
–92
.11.
Bisikirska
B
, Colgan
J
, Luban
J
, Bluestone
JA
, Herold
KC
. TCR stimulation with modified anti-CD3 mAb expands CD8+ T cell population and induces CD8+CD25+ Tregs
. J Clin Invest
. 2005
;115
(10
):2904
–13
. .12.
Vaidyanathan
S
, Barnes
M
, Williamson
P
, Hopkinson
P
, Donnan
PT
, Lipworth
B
. Treatment of chronic rhinosinusitis with nasal polyposis with oral steroids followed by topical steroids: a randomized trial
. Ann Intern Med
. 2011
;154
(5
):293
–302
. .13.
Wen
W
, Liu
W
, Zhang
L
, Bai
J
, Fan
Y
, Xia
W
, Increased neutrophilia in nasal polyps reduces the response to oral corticosteroid therapy
. J Allergy Clin Immunol
. 2012
;129
(6
):1522
–8.e5
.14.
Lin
L
, Lan
J
, Dai
F
, Wei
J
, Chen
Z
, Sun
G
. Efficacy of budesonide nasal spray on neutrophilic chronic rhinosinusitis with nasal polyps: a combined clinical and experimental study
. Int Arch Allergy Immunol
. 2020
;181
(7
):551
–62
. .15.
Ho
J
, Bailey
M
, Zaunders
J
, Bai
J
, Fan
Y
, Xia
W
, Group 2 innate lymphoid cells (ILC2s) are increased in chronic rhinosinusitis with nasal polyps or eosinophilia
. Clin Exp Allergy
. 2015
;45
(2
):394
–403
.16.
Park
SK
, Lee
WJ
, Yang
YI
. Organ culture at the air-liquid interface maintains structural and functional integrities of inflammatory and fibrovascular cells of nasal polyps
. Am J Rhinol
. 2007
;21
(4
):402
–7
. .17.
Mahdavinia
M
, Suh
LA
, Carter
RG
, Stevens
WW
, Norton
JE
, Kato
A
, Increased noneosinophilic nasal polyps in chronic rhinosinusitis in US second-generation Asians suggest genetic regulation of eosinophilia
. J Allergy Clin Immunol
. 2015
;135
(2
):576
–9
.18.
Derycke
L
, Eyerich
S
, Van Crombruggen
K
, Pérez-Novo
C
, Holtappels
G
, Deruyck
N
, Mixed T helper cell signatures in chronic rhinosinusitis with and without polyps
. PLoS One
. 2014
;9
(6
):e97581
.19.
Meltzer
EO
, Hamilos
DL
, Hadley
JA
, Lanza
DC
, Marple
BF
, Nicklas
RA
, Rhinosinusitis: establishing definitions for clinical research and patient care
. J Allergy Clin Immunol
. 2004
;114
(6 Suppl
):155
–212
.20.
Mahdavinia
M
, Carter
RG
, Ocampo
CJ
, Stevens
W
, Kato
A
, Tan
BK
, Basophils are elevated in nasal polyps of patients with chronic rhinosinusitis without aspirin sensitivity
. J Allergy Clin Immunol
. 2014
;133
(6
):1759
–63
.21.
Cao
PP
, Li
HB
, Wang
BF
, Wang
SB
, You
XJ
, Cui
YH
, Distinct immunopathologic characteristics of various types of chronic rhinosinusitis in adult Chinese
. J Allergy Clin Immunol
. 2009
;124
(3
):478
–84
. 484.e1–2.22.
Kim
SJ
, Lee
KH
, Kim
SW
, Cho
JS
, Park
YK
, Shin
SY
. Changes in histological features of nasal polyps in a Korean population over a 17-year period
. Otolaryngol Head Neck Surg
. 2013
;149
(3
):431
–7
. .23.
Nakayama
T
, Yoshikawa
M
, Asaka
D
, Okushi
T
, Matsuwaki
Y
, Otori
N
, Mucosal eosinophilia and recurrence of nasal polyps-new classification of chronic rhinosinusitis
. Rhinology
. 2011
;49
(4
):392
–6
.24.
Bateman
ND
, Shahi
A
, Feeley
KM
, Woolford
TJ
. Activated eosinophils in nasalpolyps: a comparison of asthmatic and non-asthmatic patients
. Clin Otolaryngol
. 2005
;30
(3
):221
–5
.25.
Ediger
D
, Sin
BA
, Heper
A
, Anadolu
Y
, Misirligil
Z
. Airway inflammation in nasalpolyposis: immunopathological aspects of relation to asthma
. Clin Exp Allergy
. 2005
;35
(3
):319
–26
.26.
Mao
YJ
, Chen
HH
, Wang
B
, Liu
X
, Xiong
GY
. Increased expression of MUC5AC and MUC5B promoting bacterial biofilm formation in chronic rhinosinusitis patients
. Auris Nasus Larynx
. 2015
;42
(4
):294
–8
. .27.
Tuncer
U
, Soylu
L
, Aydogan
B
, Karakus
F
, Akcali
C
. The effectiveness of steroid treatment in nasal polyposis
. Auris Nasus Larynx
. 2003
;30
(3
):263
–8
. .28.
Hissaria
P
, Smith
W
, Wormald
PJ
, Taylor
J
, Vadas
M
, Gillis
D
, Short course of systemic corticosteroids in sinonasal polyposis: a double-blind, randomized, placebo-controlled trial with evaluation of outcome measures
. J Allergy Clin Immunol
. 2006
;118
(1
):128
–33
.29.
Peric
A
, Vojvodic
D
, Matkovic-Jozin
S
. Effect of long-term, low-dose clarithromycin on T helper 2 cytokines, eosinophilic cationic protein and the “regulatedon activation, normal T cell expressed and secreted” chemokine in the nasal secretions of patients with nasal polyposis
. J Laryngol Otol
. 2012
;126
(5
):495
–502
.30.
Cowan
DC
, Cowan
JO
, Palmay
R
, Williamson
A
, Taylor
DR
. Effects of steroid therapy on inflammatory cell subtypes in asthma
. Thorax
. 2010
;65
(5
):384
–90
. .31.
Xaubet
A
, Mullol
J
, Roca-Ferrer
J
, Pujols
L
, Fuentes
M
, Pérez
M
, Effect of budesonide and nedocromil sodium on IL-6 and IL-8 release from human nasal mucosa and polyp epithelial cells
. Respir Med
. 2001
;95
(5
):408
–14
.32.
Mullol
J
, Roca-Ferrer
J
, Xaubet
A
, Raserra
J
, Picado
C
. Inhibition of GM-CSF secretion by topical corticosteroids and nedocromil sodium. A comparison study using nasal polyp epithelial cells
. Respir Med
. 2000
;94
(5
):428
–31
. .33.
Gershon
RK
, Kondo
K
. Cell interactions in the induction of tolerance: the role of thymic lymphocytes
. Immunology
. 1970
;18
(5
):723
–37
.34.
Xystrakis
E
, Dejean
AS
, Bernard
I
, Druet
P
, Liblau
R
, Gonzalez-Dunia
D
, Identification of a novel natural regulatory CD8 T-cell subset and analysis of its mechanism of regulation
. Blood
. 2004
;104
(10
):3294
–301
. .35.
Kumar
V
, Sercarz
E
. An integrative model of regulation centered on recognition of TCR peptide/MHC complexes
. Immunol Rev
. 2001
;182
:113
–21
. .36.
Kiniwa
Y
, Miyahara
Y
, Wang
HY
, Peng
W
, Peng
G
, Wheeler
TM
, CD8+ Foxp3+ regulatory T cells mediate immunosuppression in prostate cancer
. Clin Cancer Res
. 2007
;13
(23
):6947
–58
.37.
Pant
H
, Hughes
A
, Schembri
M
, Miljkovic
D
, Krumbiegel
D
. CD4+ and CD8+ regulatory T cells in chronic rhinosinusitis mucosa
. Am J Rhinol Allergy
. 2014
;28
(2
):83
–9
. .© 2022 S. Karger AG, Basel
2022
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.
