Aberrant phenotype of circulating antigen presenting cells in giant cell arteritis and polymyalgia rheumatica.
dendritic cells
giant cell arteritis
monocytes
polymyalgia rheumatica
vasculitis
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2023
2023
Historique:
received:
06
04
2023
accepted:
17
07
2023
medline:
22
8
2023
pubmed:
21
8
2023
entrez:
21
8
2023
Statut:
epublish
Résumé
Giant Cell Arteritis (GCA) and Polymyalgia Rheumatica (PMR) are overlapping inflammatory diseases. Antigen-presenting cells (APCs), including monocytes and dendritic cells (DCs), are main contributors to the immunopathology of GCA and PMR. However, little is known about APC phenotypes in the peripheral blood at the time of GCA/PMR diagnosis. APCs among peripheral blood mononuclear cells (PBMCs) of treatment-naive GCA and PMR patients were compared to those in age- and sex-matched healthy controls (HCs) using flow cytometry (n=15 in each group). We identified three monocyte subsets, and three DC subsets: plasmacytoid DCs (pDCs), CD141+ conventional DCs (cDC1) and CD1c+ conventional DCs (cDC2). Each of these subsets was analyzed for expression of pattern recognition receptors (TLR2, TLR4), immune checkpoints (CD86, PDL1, CD40) and activation markers (HLA-DR, CD11c). t-SNE plots revealed a differential clustering of APCs between GCA/PMR and HCs. Further analyses showed shifts in monocyte subsets and a lower proportion of the small population of cDC1 cells in GCA/PMR, whereas cDC2 proportions correlated negatively with CRP (r=-0.52). Classical monocytes of GCA/PMR patients show reduced expression of TLR2, HLA-DR, CD11c, which was in contrast to non-classical monocytes that showed higher marker expression. Additionally, single cell RNA sequencing in GCA patients identified a number of differentially expressed genes related to inflammation and metabolism in APCs. Circulating non-classical monocytes display an activated phenotype in GCA/PMR patients at diagnosis, whereas classical monocytes show reduced expression of activation markers. Whether these findings reflect APC migration patterns or the effects of long-term inflammation remains to be investigated.
Sections du résumé
Background
Giant Cell Arteritis (GCA) and Polymyalgia Rheumatica (PMR) are overlapping inflammatory diseases. Antigen-presenting cells (APCs), including monocytes and dendritic cells (DCs), are main contributors to the immunopathology of GCA and PMR. However, little is known about APC phenotypes in the peripheral blood at the time of GCA/PMR diagnosis.
Methods
APCs among peripheral blood mononuclear cells (PBMCs) of treatment-naive GCA and PMR patients were compared to those in age- and sex-matched healthy controls (HCs) using flow cytometry (n=15 in each group). We identified three monocyte subsets, and three DC subsets: plasmacytoid DCs (pDCs), CD141+ conventional DCs (cDC1) and CD1c+ conventional DCs (cDC2). Each of these subsets was analyzed for expression of pattern recognition receptors (TLR2, TLR4), immune checkpoints (CD86, PDL1, CD40) and activation markers (HLA-DR, CD11c).
Results
t-SNE plots revealed a differential clustering of APCs between GCA/PMR and HCs. Further analyses showed shifts in monocyte subsets and a lower proportion of the small population of cDC1 cells in GCA/PMR, whereas cDC2 proportions correlated negatively with CRP (r=-0.52). Classical monocytes of GCA/PMR patients show reduced expression of TLR2, HLA-DR, CD11c, which was in contrast to non-classical monocytes that showed higher marker expression. Additionally, single cell RNA sequencing in GCA patients identified a number of differentially expressed genes related to inflammation and metabolism in APCs.
Conclusion
Circulating non-classical monocytes display an activated phenotype in GCA/PMR patients at diagnosis, whereas classical monocytes show reduced expression of activation markers. Whether these findings reflect APC migration patterns or the effects of long-term inflammation remains to be investigated.
Identifiants
pubmed: 37600779
doi: 10.3389/fimmu.2023.1201575
pmc: PMC10433739
doi:
Substances chimiques
Toll-Like Receptor 2
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1201575Informations de copyright
Copyright © 2023 Reitsema, Hesselink, Abdulahad, van der Geest, Brouwer, Heeringa and van Sleen.
Déclaration de conflit d'intérêts
KG received a speaker fee from Roche and research funding from AbbVie paid to the UMCG. The remaining 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
Sci Immunol. 2022 Apr;7(70):eabm9409
pubmed: 35363544
Cell Death Dis. 2016 May 05;7:e2215
pubmed: 27148688
Blood. 2006 Nov 15;108(10):3580-9
pubmed: 16882710
J Exp Med. 2004 Jan 19;199(2):173-83
pubmed: 14734523
J Immunol. 2000 May 15;164(10):4991-5
pubmed: 10799849
Front Immunol. 2022 Feb 14;13:731500
pubmed: 35237256
Mucosal Immunol. 2014 Mar;7(2):440-8
pubmed: 24045574
Elife. 2021 Jul 22;10:
pubmed: 34289931
Am J Pathol. 2002 Nov;161(5):1815-23
pubmed: 12414528
J Leukoc Biol. 2003 May;73(5):639-49
pubmed: 12714579
Am J Physiol Heart Circ Physiol. 2017 May 1;312(5):H1052-H1059
pubmed: 28314758
Cell. 2020 Sep 17;182(6):1401-1418.e18
pubmed: 32810439
Front Immunol. 2018 May 09;9:755
pubmed: 29867920
Front Immunol. 2019 Aug 30;10:2035
pubmed: 31543877
Rheumatology (Oxford). 2016 Nov;55(11):1921-1931
pubmed: 26893518
Rheumatology (Oxford). 2022 Jul 6;61(7):3060-3070
pubmed: 34730794
Sci Rep. 2017 Jul 26;7(1):6553
pubmed: 28747747
Rheumatology (Oxford). 2017 Apr 1;56(4):506-515
pubmed: 27481272
Nat Rev Immunol. 2013 Apr;13(4):227-42
pubmed: 23470321
Biochem Biophys Res Commun. 2012 May 25;422(1):200-5
pubmed: 22575505
Front Immunol. 2018 Feb 22;9:315
pubmed: 29520282
Circ Res. 2015 Jul 3;117(2):129-41
pubmed: 25940549
Heliyon. 2020 Dec;6(12):e05635
pubmed: 33283062
Sci Rep. 2015 Sep 11;5:13886
pubmed: 26358827
J Am Coll Cardiol. 2006 Jul 4;48(1):70-80
pubmed: 16814651
Int Immunol. 2019 Oct 16;31(11):687-696
pubmed: 31063541
Blood. 2017 Sep 21;130(12):1474-1477
pubmed: 28743715
Arthritis Rheum. 2001 Feb;44(2):419-31
pubmed: 11229474
Ann Rheum Dis. 2023 Mar;82(3):440-442
pubmed: 35961758
Sci Rep. 2021 May 27;11(1):11248
pubmed: 34045571
Front Immunol. 2022 Aug 11;13:943574
pubmed: 36032100
Immunol Cell Biol. 2018 May;96(5):463-476
pubmed: 29473216
Int Immunopharmacol. 2022 Jul;108:108697
pubmed: 35405594
Rheumatology (Oxford). 2019 Jan 1;58(1):154-164
pubmed: 30204915
Autoimmun Rev. 2017 Aug;16(8):833-844
pubmed: 28564617
Nat Immunol. 2007 Mar;8(3):239-45
pubmed: 17304234
Rheumatology (Oxford). 2022 Dec 23;62(1):417-427
pubmed: 35460236
Nat Rev Rheumatol. 2023 Jul;19(7):446-459
pubmed: 37308659
Cell Mol Life Sci. 2015 Jun;72(12):2349-60
pubmed: 25715742
Immunity. 2019 Jan 15;50(1):37-50
pubmed: 30650380
J Immunol. 2018 Dec 15;201(12):3534-3545
pubmed: 30404814
Immunology. 2018 May;154(1):3-20
pubmed: 29313948
Medicina (Kaunas). 2022 Sep 01;58(9):
pubmed: 36143874
Arthritis Res Ther. 2022 Mar 7;24(1):65
pubmed: 35255968