Leukocyte toll-like receptor expression in pathergy positive and negative Behçet's disease patients.
Adult
B-Lymphocytes
/ metabolism
Behcet Syndrome
/ metabolism
CD4-Positive T-Lymphocytes
/ metabolism
CD8-Positive T-Lymphocytes
/ metabolism
Case-Control Studies
Female
Flow Cytometry
Humans
Male
Middle Aged
Toll-Like Receptor 1
/ metabolism
Toll-Like Receptor 2
/ metabolism
Toll-Like Receptor 4
/ metabolism
Toll-Like Receptors
/ metabolism
Young Adult
Behçet’s disease
TLR
flagellin
innate immune system
pathergy
Journal
Rheumatology (Oxford, England)
ISSN: 1462-0332
Titre abrégé: Rheumatology (Oxford)
Pays: England
ID NLM: 100883501
Informations de publication
Date de publication:
01 Dec 2020
01 Dec 2020
Historique:
received:
21
05
2019
revised:
15
04
2020
pubmed:
7
8
2020
medline:
28
1
2021
entrez:
7
8
2020
Statut:
ppublish
Résumé
To investigate whether the auto-inflammatory nature and the pathergic reaction in Behçet's disease (BD) are driven by a disturbed toll-like receptor (TLR) response. We compared both TLR expression by flow-cytometry and TLR response by stimulation assay in 18 BD patients (both pathergy positive and pathergy negative) with 15 healthy controls. Expression of TLR1 and 2 was significantly elevated in B-lymphocytes of BD patients compared with healthy controls. TLR1, 2 and 4 were significantly more highly expressed in both CD4+ and CD8+ T-lymphocytes of BD patients. Granulocytes of BD patients displayed significantly higher expression of TLR1, 2, 4 and 6. TLR2, 4 and 5 expression was significantly increased on classical monocytes of BD patients. Intermediate monocytes of BD patients showed an increase in expression of TLR2. Furthermore, TLR2 and 5 were significantly more highly expressed in non-classical monocytes of BD patients. In pathergy positive patients, TLR5 was even more highly expressed compared with pathergy negative patients on B- and T-lymphocytes and granulocytes. Furthermore, TLR2 and 5 showed an elevated TNF-α response to stimulation with their cognate ligands. Immune cells of BD patients overexpress TLR1, 2, 4, 5 and 6. Furthermore, after stimulation of TLR2 and 5, BD patients demonstrate a more potent TNF-α response. Although this is a small cohort, in the pathergy positive patients, TLR5 expression is even further augmented, suggesting that a microbial (flagellin) or damage (HMGB1) associated signal may trigger the exaggerated immune response that is characteristic for the pathergy phenomenon in BD. In conclusion, these results point to an exaggerated TLR response in the auto-inflammatory nature of BD.
Identifiants
pubmed: 32756992
pii: 5881460
doi: 10.1093/rheumatology/keaa251
pmc: PMC7733715
doi:
Substances chimiques
TLR1 protein, human
0
TLR2 protein, human
0
TLR4 protein, human
0
Toll-Like Receptor 1
0
Toll-Like Receptor 2
0
Toll-Like Receptor 4
0
Toll-Like Receptors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3971-3979Informations de copyright
© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.
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