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Immunomodulatory role of Interleukin-33 in large vessel vasculitis.

Authors :
Desbois AC
Cacoub P
Leroyer AS
Tellier E
Garrido M
Maciejewski-Duval A
Comarmond C
Barete S
Arock M
Bruneval P
Launay JM
Fouret P
Blank U
Rosenzwajg M
Klatzmann D
Jarraya M
Cluzel P
Koskas F
Kaplanski G
Saadoun D
Source :
Scientific reports [Sci Rep] 2020 Apr 14; Vol. 10 (1), pp. 6405. Date of Electronic Publication: 2020 Apr 14.
Publication Year :
2020

Abstract

The mechanisms regulating inflammation in large vessels vasculitis (LVV) are poorly understood. Interleukin 33 (IL-33) has been shown to license innate and adaptive immunity by enhancing Th2 cytokines production. We aimed to examine the role of IL-33 in the immunomodulation of T cell activation in LVV. T cell homeostasis and cytokines production were determined in peripheral blood from 52 patients with giant cell arteritis (GCA) and 50 healthy donors (HD), using Luminex assay, flow cytometry, quantitative RT-PCR and by immunofluorescence analysis in inflammatory aorta lesions. We found increased level of IL-33 and its receptor ST2/IL-1R4 in the serum of patient with LVV. Endothelial cells were the main source of IL-33, whereas Th2 cells, Tregs and mast cells (MC) express ST2 in LVV vessels. IL-33 had a direct immunomodulatory impact by increasing Th2 and Tregs. IL-33 and MC further enhanced Th2 and regulatory responses by inducing a 6.1 fold increased proportion of Tregs (p = 0.008). Stimulation of MC by IL-33 increased indoleamine 2 3-dioxygenase (IDO) activity and IL-2 secretion. IL-33 mRNA expression was significantly correlated with the expression of IL-10 and TGF-β within aorta inflammatory lesions. To conclude, our findings suggest that IL-33 may exert a critical immunoregulatory role in promoting Tregs and Th2 cells in LVV.

Details

Language :
English
ISSN :
2045-2322
Volume :
10
Issue :
1
Database :
MEDLINE
Journal :
Scientific reports
Publication Type :
Academic Journal
Accession number :
32286393
Full Text :
https://doi.org/10.1038/s41598-020-63042-3