Clickable Vitamins as a New Tool to Track Vitamin A and Retinoic Acid in Immune Cells.
CD38
copper-facilitated click chemistry
retinoic acid
retinoid probes
vitamin A metabolism
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
23
02
2021
accepted:
02
06
2021
entrez:
26
7
2021
pubmed:
27
7
2021
medline:
3
11
2021
Statut:
epublish
Résumé
The vitamin A derivative, retinoid acid (RA) is key player in guiding adaptive mucosal immune responses. However, data on the uptake and metabolism of vitamin A within human immune cells has remained largely elusive because retinoids are small, lipophilic molecules which are difficult to detect. To overcome this problem and to be able to study the effect of vitamin A metabolism in human immune cell subsets, we have synthesized novel bio-orthogonal retinoid-based probes (clickable probes), which are structurally and functionally indistinguishable from vitamin A. The probes contain a functional group (an alkyne) to conjugate to a fluorogenic dye to monitor retinoid molecules in real-time in immune cells. We demonstrate, by using flow cytometry and microscopy, that multiple immune cells have the capacity to internalize retinoids to varying degrees, including human monocyte-derived dendritic cells (DCs) and naïve B lymphocytes. We observed that naïve B cells lack the enzymatic machinery to produce RA, but use exogenous retinoic acid to enhance CD38 expression. Furthermore, we showed that human DCs metabolize retinal into retinoic acid, which in co-culture with naïve B cells led to of the induction of CD38 expression. These data demonstrate that in humans, DCs can serve as an exogenous source of RA for naïve B cells. Taken together, through the use of clickable vitamins our data provide valuable insight in the mechanism of vitamin A metabolism and its importance for human adaptive immunity.
Identifiants
pubmed: 34305901
doi: 10.3389/fimmu.2021.671283
pmc: PMC8298001
doi:
Substances chimiques
Fluorescent Dyes
0
Vitamin A
11103-57-4
Tretinoin
5688UTC01R
Copper
789U1901C5
ADP-ribosyl Cyclase 1
EC 3.2.2.6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
671283Informations de copyright
Copyright © 2021 Bos, Erkelens, Koenders, van der Stelt, van Egmond and Mebius.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
J Am Chem Soc. 2018 May 16;140(19):6067-6075
pubmed: 29420021
Mol Biotechnol. 1998 Oct;10(2):167-82
pubmed: 9819815
J Lipid Res. 2013 Aug;54(8):2282-2290
pubmed: 23709689
Chem Biol Interact. 2003 Feb 1;143-144:201-10
pubmed: 12604205
J Biol Chem. 2008 Sep 26;283(39):26684-93
pubmed: 18658157
Hum Immunol. 2014 Aug;75(8):923-9
pubmed: 24994461
J Immunol. 2015 Aug 15;195(4):1368-71
pubmed: 26163586
Eur J Immunol. 2015 Jan;45(1):89-100
pubmed: 25311225
J Clin Med. 2018 Sep 06;7(9):
pubmed: 30200565
Gastroenterology. 2011 Jul;141(1):176-85
pubmed: 21596042
Genes Dev. 2007 May 1;21(9):1113-24
pubmed: 17473173
Int Immunopharmacol. 2005 Dec;5(13-14):1830-8
pubmed: 16275619
J Biol Chem. 2009 May 29;284(22):15173-83
pubmed: 19304658
J Leukoc Biol. 2017 May;101(5):1169-1180
pubmed: 28087652
Science. 2006 Nov 17;314(5802):1157-60
pubmed: 17110582
Cell Mol Immunol. 2016 Nov;13(6):862-870
pubmed: 26277894
Clin Infect Dis. 2017 Sep 15;65(6):900-909
pubmed: 28531276
ACS Chem Biol. 2011 Oct 21;6(10):1041-51
pubmed: 21774515
Nutr Rev. 1994 Feb;52(2 Pt 2):S13-23
pubmed: 8202278
Br J Nutr. 2005 Jan;93(1):59-63
pubmed: 15705226
ACS Chem Biol. 2012 Dec 21;7(12):2004-11
pubmed: 22999348
J Exp Med. 2008 Oct 27;205(11):2483-90
pubmed: 18852290
J Exp Med. 2007 Aug 6;204(8):1775-85
pubmed: 17620362
Immunity. 2004 Oct;21(4):527-38
pubmed: 15485630
ACS Chem Biol. 2009 Jul 17;4(7):581-7
pubmed: 19505150
J Exp Med. 2008 Sep 1;205(9):2139-49
pubmed: 18710932
J Immunol. 2009 Nov 15;183(10):6395-402
pubmed: 19841174
Mucosal Immunol. 2015 Mar;8(2):265-78
pubmed: 25027601
Mucosal Immunol. 2016 Jan;9(1):171-82
pubmed: 26080709
Nutrients. 2016 Jun 13;8(6):
pubmed: 27304965
J Immunol. 2011 Feb 15;186(4):1934-42
pubmed: 21220692
Trends Immunol. 2012 Jan;33(1):42-8
pubmed: 22079120
J Lipid Res. 2016 Oct;57(10):1934-1947
pubmed: 27565170
Nat Immunol. 2014 Jan;15(1):98-108
pubmed: 24292363
J Leukoc Biol. 2013 Aug;94(2):325-35
pubmed: 23744644
Science. 2007 Feb 9;315(5813):820-5
pubmed: 17255476
Biochim Biophys Acta. 2012 Jan;1821(1):70-7
pubmed: 21718801
Nestle Nutr Inst Workshop Ser. 2012;70:79-90
pubmed: 25825298
Mucosal Immunol. 2018 May;11(3):703-715
pubmed: 29139475
J Lipid Res. 1965 Jul;6:390-6
pubmed: 14336210
J Lipid Res. 2016 Oct;57(10):1821-1830
pubmed: 27538823
Mucosal Immunol. 2008 Jan;1(1):38-48
pubmed: 19079159
J Biol Chem. 2008 Apr 11;283(15):9543-54
pubmed: 18195010
Membranes (Basel). 2015 Aug 28;5(3):425-53
pubmed: 26343735
Eur J Immunol. 2018 Feb;48(2):283-292
pubmed: 28921509
Eur J Haematol. 2017 Jan;98(1):19-25
pubmed: 27199264
J Pharmacol Exp Ther. 2017 May;361(2):246-258
pubmed: 28275201
Gut. 2009 Nov;58(11):1481-9
pubmed: 19570762
PLoS One. 2013 Dec 06;8(12):e82121
pubmed: 24324757
J Exp Med. 2007 Aug 6;204(8):1757-64
pubmed: 17620361
ACS Cent Sci. 2019 Dec 26;5(12):1965-1974
pubmed: 31893226
J Periodontal Implant Sci. 2014 Oct;44(5):235-41
pubmed: 25368812
J Immunol. 2006 Jan 15;176(2):803-10
pubmed: 16393963
J Exp Med. 2005 Oct 17;202(8):1063-73
pubmed: 16216890
J Lipid Res. 2018 Dec;59(12):2446-2455
pubmed: 30266834
Sci Rep. 2019 Nov 25;9(1):17508
pubmed: 31767918
Am J Pathol. 2012 Mar;180(3):984-997
pubmed: 22222225
Vitam Horm. 2011;86:103-26
pubmed: 21419269