Alum impairs tolerogenic properties induced by allergoid-mannan conjugates inhibiting mTOR and metabolic reprogramming in human DCs.
allergen-specific immunotherapy
alum
dendritic cells
polymerized allergoids conjugated to mannan
regulatory T cells
Journal
Allergy
ISSN: 1398-9995
Titre abrégé: Allergy
Pays: Denmark
ID NLM: 7804028
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
21
05
2019
revised:
26
07
2019
accepted:
16
08
2019
pubmed:
9
9
2019
medline:
15
5
2021
entrez:
9
9
2019
Statut:
ppublish
Résumé
Polymerized allergoids conjugated to mannan (PM) are suitable vaccines for allergen-specific immunotherapy (AIT). Alum remains the most widely used adjuvant in AIT, but its way of action is not completely elucidated. The better understanding of the mechanisms underlying alum adjuvanticity could help to improve AIT vaccine formulations. We sought to investigate the potential influence of alum in the tolerogenic properties imprinted by PM at the molecular level. Flow cytometry, ELISAs, cocultures, intracellular staining and suppression assays were performed to assess alum and PM effects in human dendritic cells (DCs). BALB/c mice were immunized with PM alone or adsorbed to alum. Allergen-specific antibodies, splenocyte cytokine production and splenic forkhead box P3 (FOXP3) Alum decreases PD-L1 expression and IL-10 production induced by PM in human DCs and increases pro-inflammatory cytokine production. Alum impairs PM-induced functional FOXP3 We uncover novel mechanisms by which alum impairs the tolerogenic properties induced by PM, which might well contribute to improve the formulation of novel vaccines for AIT.
Sections du résumé
BACKGROUND
Polymerized allergoids conjugated to mannan (PM) are suitable vaccines for allergen-specific immunotherapy (AIT). Alum remains the most widely used adjuvant in AIT, but its way of action is not completely elucidated. The better understanding of the mechanisms underlying alum adjuvanticity could help to improve AIT vaccine formulations.
OBJECTIVE
We sought to investigate the potential influence of alum in the tolerogenic properties imprinted by PM at the molecular level.
METHODS
Flow cytometry, ELISAs, cocultures, intracellular staining and suppression assays were performed to assess alum and PM effects in human dendritic cells (DCs). BALB/c mice were immunized with PM alone or adsorbed to alum. Allergen-specific antibodies, splenocyte cytokine production and splenic forkhead box P3 (FOXP3)
RESULTS
Alum decreases PD-L1 expression and IL-10 production induced by PM in human DCs and increases pro-inflammatory cytokine production. Alum impairs PM-induced functional FOXP3
CONCLUSION
We uncover novel mechanisms by which alum impairs the tolerogenic properties induced by PM, which might well contribute to improve the formulation of novel vaccines for AIT.
Identifiants
pubmed: 31494959
doi: 10.1111/all.14036
pmc: PMC7079174
doi:
Substances chimiques
Allergoids
0
Alum Compounds
0
Mannans
0
aluminum sulfate
34S289N54E
MTOR protein, human
EC 2.7.1.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
648-659Informations de copyright
© 2020 The Authors. Allergy published by John Wiley & Sons Ltd.
Références
Nat Rev Immunol. 2015 Oct;15(10):599-614
pubmed: 26403194
FEBS Lett. 2017 Oct;591(19):3089-3103
pubmed: 28600802
Trends Immunol. 2016 Nov;37(11):778-789
pubmed: 27614799
Expert Rev Clin Immunol. 2017 Jun;13(6):599-610
pubmed: 28162007
J Allergy Clin Immunol. 2017 Dec;140(6):1485-1498
pubmed: 29221580
Allergy. 2017 Nov;72(11):1597-1631
pubmed: 28493631
EMBO J. 2010 Dec 15;29(24):4118-31
pubmed: 21113129
Cell Rep. 2018 Oct 30;25(5):1118-1126
pubmed: 30380404
Nat Med. 2011 Jul 17;17(8):996-1002
pubmed: 21765404
Allergy. 2018 Jan;73 Suppl 104:5-23
pubmed: 29171712
Front Immunol. 2018 May 31;9:1169
pubmed: 29904379
J Exp Med. 2009 Dec 21;206(13):3015-29
pubmed: 20008522
Nat Rev Drug Discov. 2019 Jul;18(7):553-566
pubmed: 30967658
World Allergy Organ J. 2015 Feb 28;8(1):7
pubmed: 25780491
J Allergy Clin Immunol. 2016 Aug;138(2):568-70
pubmed: 27497282
PLoS One. 2017 Apr 20;12(4):e0175549
pubmed: 28426686
Glycoconj J. 2016 Feb;33(1):93-101
pubmed: 26603537
Trends Immunol. 2002 Jun;23(6):273-5
pubmed: 12072358
Allergo J Int. 2018;27(8):256-262
pubmed: 30546997
J Immunol. 2018 Sep 1;201(5):1510-1521
pubmed: 30037846
Allergy. 2018 Apr;73(4):875-884
pubmed: 29319882
Allergy. 2017 Feb;72(2):221-231
pubmed: 27138374
Eur Respir J. 2015 Mar;45(3):790-806
pubmed: 25614163
Front Immunol. 2018 Dec 17;9:2936
pubmed: 30619296
Nat Med. 2011 Apr;17(4):479-87
pubmed: 21399646
Nat Med. 2014 Jun;20(6):642-7
pubmed: 24813249
Immune Netw. 2016 Feb;16(1):52-60
pubmed: 26937232
J Allergy Clin Immunol. 2011 Dec;128(6):1369-71
pubmed: 21868077
Allergy. 2018 Dec;73(12):2274-2289
pubmed: 30372537
Nat Rev Immunol. 2015 Jan;15(1):18-29
pubmed: 25534620
Front Immunol. 2013 Jan 10;3:406
pubmed: 23335921
Immunology. 2014 Mar;141(3):467-81
pubmed: 24708420
J Allergy Clin Immunol. 2016 Feb;137(2):358-68
pubmed: 26853128
Allergy. 2009 Jun;64(6):890-7
pubmed: 19210370
Nat Med. 2017 Sep;23(9):1036-1045
pubmed: 28759052
Immunol Rev. 2017 Jul;278(1):219-236
pubmed: 28658547
Allergy. 2020 Mar;75(3):648-659
pubmed: 31494959
Vet Immunol Immunopathol. 2017 Aug;190:65-72
pubmed: 28778325
Allergy. 2019 Nov;74(11):2087-2102
pubmed: 30955224
J Allergy Clin Immunol. 2019 Mar;143(3):813-828
pubmed: 30850069
Hum Vaccin Immunother. 2012 Oct;8(10):1492-8
pubmed: 23095872
Leukemia. 2011 Jun;25(6):960-7
pubmed: 21455214
J Allergy Clin Immunol. 2017 Nov;140(5):1250-1267
pubmed: 28941667
Trends Immunol. 2018 Jun;39(6):489-502
pubmed: 29452982
Curr Opin Immunol. 2014 Jun;28:1-5
pubmed: 24463269
J Exp Med. 2005 Nov 7;202(9):1213-23
pubmed: 16275760
J Immunol. 2015 Jun 1;194(11):5174-86
pubmed: 25917094
J Immunol. 2007 Sep 15;179(6):3515-23
pubmed: 17785785
Curr Opin Immunol. 2017 Jun;46:103-111
pubmed: 28535458
J Allergy Clin Immunol. 2018 May;141(5):1786-1798.e11
pubmed: 28886863
Nat Rev Immunol. 2016 Sep;16(9):553-65
pubmed: 27396447
J Med Microbiol. 2012 Jul;61(Pt 7):927-934
pubmed: 22174375
J Allergy Clin Immunol. 2016 Aug;138(2):558-567.e11
pubmed: 27177779
Blood. 2009 Mar 26;113(13):2934-44
pubmed: 19136659
J Exp Med. 2016 Jan 11;213(1):15-23
pubmed: 26694970