Monocyte-derived dendritic cells display a highly activated phenotype and altered function in patients with familial Mediterranean fever.


Journal

Clinical and experimental immunology
ISSN: 1365-2249
Titre abrégé: Clin Exp Immunol
Pays: England
ID NLM: 0057202

Informations de publication

Date de publication:
07 2020
Historique:
received: 16 07 2019
revised: 31 03 2020
accepted: 01 04 2020
pubmed: 12 4 2020
medline: 21 10 2020
entrez: 12 4 2020
Statut: ppublish

Résumé

Dendritic cells (DCs) are sentinels of the immune system that bridge innate and adaptive immunity. By capturing antigens in peripheral tissue, processing and presenting them with concurrent expression of co-stimulatory molecules and cytokine secretion they control and modulate immune reactions. Through pattern recognition receptors, DCs sense molecules that are associated with infection or tissue damage, frequently resulting in the formation of inflammasomes upon intracellular stimulation. The inherited autoinflammatory familial Mediterranean fever (FMF) is associated with deregulated activity of the pyrin inflammasome leading to acute inflammatory episodes. However, differentiation and function of DCs in this disease are as yet unclear. Therefore, we first determined DC subpopulation frequency in peripheral blood of a cohort of FMF patients. Joint evaluation without classification according to specific patient characteristics, such as mutational status, did not disclose significant differences compared to healthy controls. For the further examination of phenotype and function, we used immature and mature monocyte-derived DCs (imMo-DCs, mMo-DCs) that were generated in vitro from FMF patients. Immunophenotypical analysis of imMo-DCs revealed a significantly elevated expression of CD83, CD86 and human leukocyte antigen D-related (HLA-DR) as well as a significant down-regulation of CD206, CD209 and glycoprotein NMB (GPNMB) in our FMF patient group. Furthermore, FMF imMo-DCs presented a significantly higher capacity to migrate and to stimulate the proliferation of unmatched allogeneic T cells. Finally, the transition towards a more mature, and therefore activated, phenotype was additionally reinforced by the fact that peripheral blood DC populations in FMF patients exhibited significantly increased expression of the co-stimulatory molecule CD86.

Identifiants

pubmed: 32278322
doi: 10.1111/cei.13439
pmc: PMC7290084
doi:

Substances chimiques

Antigens, Differentiation 0

Types de publication

Clinical Trial Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1-11

Informations de copyright

© 2020 The Authors. Clinical & Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology.

Références

Clin Rheumatol. 2012 May;31(5):885-8
pubmed: 22234494
Nat Genet. 1997 Sep;17(1):25-31
pubmed: 9288094
Annu Rev Immunol. 2003;21:335-76
pubmed: 12524386
Nat Immunol. 2016 Aug;17(8):914-21
pubmed: 27270401
Front Immunol. 2017 Jan 27;8:43
pubmed: 28191008
Cancer Immunol Immunother. 2018 May;67(5):775-783
pubmed: 29468363
Cancer Immunol Immunother. 2012 Feb;61(2):193-202
pubmed: 21874302
Arthritis Res. 2002;4 Suppl 3:S127-32
pubmed: 12110131
Arthritis Rheum. 1997 Oct;40(10):1879-85
pubmed: 9336425
Nature. 2014 Sep 11;513(7517):237-41
pubmed: 24919149
Blood. 2000 May 15;95(10):3223-31
pubmed: 10807793
Immunol Rev. 2007 Oct;219:118-42
pubmed: 17850486
Leukemia. 2009 Mar;23(3):535-44
pubmed: 19005481
Clin Exp Immunol. 2004 Dec;138(3):526-33
pubmed: 15544632
Eur J Immunol. 2018 Feb;48(2):230-238
pubmed: 29148036
Nature. 1998 Mar 19;392(6673):245-52
pubmed: 9521319
Cell Commun Signal. 2015 Mar 24;13:19
pubmed: 25889792
Nat Immunol. 2004 Oct;5(10):987-95
pubmed: 15454922
Open Access Maced J Med Sci. 2018 Feb 09;6(2):310-313
pubmed: 29531594
Nat Rev Immunol. 2013 Aug;13(8):566-77
pubmed: 23827956
Front Immunol. 2017 Mar 23;8:253
pubmed: 28386255
J Exp Med. 1998 Jul 20;188(2):373-86
pubmed: 9670049
Cell Mol Life Sci. 2015 Nov;72(22):4309-25
pubmed: 26243730
Annu Rev Immunol. 2000;18:767-811
pubmed: 10837075
Ann Rheum Dis. 2018 Nov;77(11):1558-1565
pubmed: 30100561
Immunity. 2011 May 27;34(5):755-68
pubmed: 21600797
Nat Rev Immunol. 2016 Jul;16(7):407-20
pubmed: 27291964
Proc Natl Acad Sci U S A. 2016 Aug 16;113(33):E4857-66
pubmed: 27482109
Cytokine Growth Factor Rev. 2008 Feb;19(1):41-52
pubmed: 18258476
Immunology. 2013 Sep;140(1):22-30
pubmed: 23621371
Cell. 2016 May 5;165(4):792-800
pubmed: 27153493
Cell. 1997 Aug 22;90(4):797-807
pubmed: 9288758

Auteurs

T Funk (T)

Department of Medical Oncology, Haematology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany.

A R Fuchs (AR)

Department of Medical Oncology, Haematology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany.

V S Altdörfer (VS)

Department of Medical Oncology, Haematology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany.

R Klein (R)

Department of Medical Oncology, Haematology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany.

S E Autenrieth (SE)

Department of Medical Oncology, Haematology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany.

M R Müller (MR)

Department of Medical Oncology, Haematology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany.

H R Salih (HR)

Department of Medical Oncology, Haematology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany.
2Clinical Collaboration Unit (CCU) Translational Immunology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Partner Site Tübingen, Tübingen, Germany.

J Henes (J)

Department of Medical Oncology, Haematology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany.

F Grünebach (F)

Department of Medical Oncology, Haematology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany.

D Dörfel (D)

Department of Medical Oncology, Haematology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany.
2Clinical Collaboration Unit (CCU) Translational Immunology, German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Partner Site Tübingen, Tübingen, Germany.

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