Low oxygen levels decrease adaptive immune responses and ameliorate experimental asthma in mice.
MHC-II
allergy
asthma
dendritic cells
hypoxia
Journal
Allergy
ISSN: 1398-9995
Titre abrégé: Allergy
Pays: Denmark
ID NLM: 7804028
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
revised:
09
06
2021
received:
12
01
2021
accepted:
13
07
2021
pubmed:
27
7
2021
medline:
9
4
2022
entrez:
26
7
2021
Statut:
ppublish
Résumé
High-altitude therapy has been used as add-on treatment for allergic asthma with considerable success. However, the underlying mechanisms remain unclear. In order to investigate the possible therapeutic effects of high-altitude therapy on allergic asthma, we utilized a new in vivo mouse model. Mice were treated with house dust mite (HDM) extract over 4 weeks and co-exposed to 10% oxygen (Hyp) or room air for the final 2 weeks. Experimental asthma was assessed by airway hyper-responsiveness, mucus hypersecretion and inflammatory cell recruitment. Isolated immune cells from mouse and allergic patients were stimulated in vitro with HDM under Hyp and normoxia in different co-culture systems to analyse the adaptive immune response. Compared to HDM-treated mice in room air, HDM-treated Hyp-mice displayed ameliorated mucosal hypersecretion and airway hyper-responsiveness. The attenuated asthma phenotype was associated with strongly reduced activation of antigen-presenting cells (APCs), effector cell infiltration and cytokine secretion. In vitro, hypoxia almost completely suppressed the HDM-induced adaptive immune response in both mouse and human immune cells. While hypoxia did not affect effector T-cell responses per-se, it interfered with antigen-presenting cell (APC) differentiation and APC/effector cell crosstalk. Hypoxia-induced reduction in the Th2-response to HDM ameliorates allergic asthma in vivo. Hypoxia interferes with APC/T-cell crosstalk and confers an unresponsive phenotype to APCs.
Sections du résumé
BACKGROUND
High-altitude therapy has been used as add-on treatment for allergic asthma with considerable success. However, the underlying mechanisms remain unclear. In order to investigate the possible therapeutic effects of high-altitude therapy on allergic asthma, we utilized a new in vivo mouse model.
METHODS
Mice were treated with house dust mite (HDM) extract over 4 weeks and co-exposed to 10% oxygen (Hyp) or room air for the final 2 weeks. Experimental asthma was assessed by airway hyper-responsiveness, mucus hypersecretion and inflammatory cell recruitment. Isolated immune cells from mouse and allergic patients were stimulated in vitro with HDM under Hyp and normoxia in different co-culture systems to analyse the adaptive immune response.
RESULTS
Compared to HDM-treated mice in room air, HDM-treated Hyp-mice displayed ameliorated mucosal hypersecretion and airway hyper-responsiveness. The attenuated asthma phenotype was associated with strongly reduced activation of antigen-presenting cells (APCs), effector cell infiltration and cytokine secretion. In vitro, hypoxia almost completely suppressed the HDM-induced adaptive immune response in both mouse and human immune cells. While hypoxia did not affect effector T-cell responses per-se, it interfered with antigen-presenting cell (APC) differentiation and APC/effector cell crosstalk.
CONCLUSIONS
Hypoxia-induced reduction in the Th2-response to HDM ameliorates allergic asthma in vivo. Hypoxia interferes with APC/T-cell crosstalk and confers an unresponsive phenotype to APCs.
Identifiants
pubmed: 34309864
doi: 10.1111/all.15020
pmc: PMC9290649
doi:
Substances chimiques
Allergens
0
Oxygen
S88TT14065
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
870-882Informations de copyright
© 2021 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
Références
Clin Exp Allergy. 1993 Dec;23(12):1021-6
pubmed: 10779296
Allergy. 2022 Mar;77(3):870-882
pubmed: 34309864
Pflugers Arch. 2009 Nov;459(1):93-103
pubmed: 19641936
Ann Am Thorac Soc. 2018 Mar;15(3):348-356
pubmed: 29323930
Eur Respir J. 1995 Mar;8(3):357-63
pubmed: 7789477
Pediatr Pulmonol. 1994 May;17(5):304-11
pubmed: 8058424
Med Microbiol Immunol. 2020 Aug;209(4):515-529
pubmed: 32451606
Br Med J. 1971 Jan 9;1(5740):82-4
pubmed: 5539181
Am J Pathol. 2009 Dec;175(6):2454-62
pubmed: 19850888
Am J Respir Crit Care Med. 2010 Feb 15;181(4):394-418
pubmed: 20130146
Cell. 2003 Mar 7;112(5):645-57
pubmed: 12628185
J Immunol. 2012 Aug 15;189(4):1955-65
pubmed: 22786772
Am J Respir Cell Mol Biol. 2015 Feb;52(2):162-70
pubmed: 25004109
NPJ Prim Care Respir Med. 2019 Oct 21;29(1):37
pubmed: 31636268
Scand J Immunol. 2006 Apr;63(4):304-10
pubmed: 16623931
N Engl J Med. 2006 Nov 23;355(21):2226-35
pubmed: 17124020
Eur J Immunol. 2008 Jun;38(6):1631-42
pubmed: 18493983
J Allergy Clin Immunol. 2016 Mar;137(3):833-43
pubmed: 26792210
J Immunol Methods. 2006 Jan 20;308(1-2):179-91
pubmed: 16406060
PLoS One. 2013;8(1):e55180
pubmed: 23383100
J Allergy Clin Immunol. 1996 Jul;98(1):64-72
pubmed: 8765819
J Allergy Clin Immunol Pract. 2018 May - Jun;6(3):776-781
pubmed: 29408385
J Allergy Clin Immunol. 2007 Feb;119(2):297-302
pubmed: 17291849
PLoS One. 2014 Jan 21;9(1):e85839
pubmed: 24465740
Clin Exp Allergy. 2016 Jun;46(6):825-36
pubmed: 27079298
Respir Med. 2020 Sep;171:106123
pubmed: 32846334
Respir Med Res. 2021 May;79:100810
pubmed: 33540154
Nat Rev Immunol. 2014 Jun;14(6):392-404
pubmed: 24854589
J Immunol. 2012 Aug 15;189(4):1946-54
pubmed: 22778395
Front Immunol. 2018 Sep 05;9:2018
pubmed: 30233597
J Leukoc Biol. 2007 Nov;82(5):1257-65
pubmed: 17675562
Int Immunopharmacol. 2016 May;34:1-15
pubmed: 26906720
Lancet. 2000 Sep 16;356(9234):982-7
pubmed: 11041399
J Allergy Clin Immunol. 2015 Apr;135(4):896-902
pubmed: 25441637
ERJ Open Res. 2016 Jun 06;2(2):
pubmed: 27730196
Am J Respir Crit Care Med. 2020 Feb 1;201(3):276-293
pubmed: 31525297
Sleep Breath. 2020 Jun;24(2):523-532
pubmed: 31302837
J Allergy Clin Immunol. 1982 Mar;69(3):290-6
pubmed: 7061770
Antioxid Redox Signal. 2017 Dec 20;27(18):1460-1472
pubmed: 28510479