Immunomodulatory role of Interleukin-33 in large vessel vasculitis
Anne-Claire Desbois
(1, 2, 2)
,
Patrice Cacoub
(1, 2, 2)
,
Aurélie S. Leroyer
(3, 4)
,
Edwige Tellier
(3, 4)
,
Marlène Garrido
(1, 2)
,
Anna Maciejewski-Duval
(1, 2)
,
Cloé Comarmond
(1, 2, 2)
,
Stéphane Barète
(2)
,
Michel Arock
(2)
,
Patrick Bruneval
(5)
,
Jean-Marie Launay
(6)
,
Pierre Fouret
(2)
,
Ulrich Blank
(7)
,
Michelle Rosenzwajg
(1, 2, 2)
,
David Klatzmann
(1, 2, 2)
,
Mohamed Jarraya
(8)
,
Philippe Cluzel
(2)
,
Fabien Koskas
(2)
,
Gilles Kaplanski
(2, 9, 4)
,
David Saadoun
(1, 2, 2)
1
I3 -
Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière]
2 CHU Pitié-Salpêtrière [AP-HP]
3 VRCM - Vascular research center of Marseille
4 C2VN - Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research
5 HEGP - Hôpital Européen Georges Pompidou [APHP]
6 MASCOT (UMR_S_942 / U942) - Marqueurs cardiovasculaires en situation de stress
7 CRI (UMR_S_1149 / ERL_8252 / U1149) - Centre de recherche sur l'Inflammation
8 AP-HP - Hopital Saint-Louis [AP-HP]
9 LA CONCEPTION - Hôpital de la Conception [CHU - APHM]
2 CHU Pitié-Salpêtrière [AP-HP]
3 VRCM - Vascular research center of Marseille
4 C2VN - Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research
5 HEGP - Hôpital Européen Georges Pompidou [APHP]
6 MASCOT (UMR_S_942 / U942) - Marqueurs cardiovasculaires en situation de stress
7 CRI (UMR_S_1149 / ERL_8252 / U1149) - Centre de recherche sur l'Inflammation
8 AP-HP - Hopital Saint-Louis [AP-HP]
9 LA CONCEPTION - Hôpital de la Conception [CHU - APHM]
Patrice Cacoub
- Function : Author
- PersonId : 923051
Edwige Tellier
- Function : Author
- PersonId : 1234659
- IdHAL : edwige-tellier
- ORCID : 0000-0003-3044-5388
Patrick Bruneval
- Function : Author
- PersonId : 756352
- ORCID : 0000-0002-2350-2914
Jean-Marie Launay
- Function : Author
- PersonId : 757247
- ORCID : 0000-0003-4809-1020
Ulrich Blank
- Function : Author
- PersonId : 767849
- ORCID : 0000-0002-2661-2983
- IdRef : 073330329
Michelle Rosenzwajg
- Function : Author
- PersonId : 934586
David Klatzmann
- Function : Author
- PersonId : 757052
- ORCID : 0000-0002-0054-3422
- IdRef : 069959846
David Saadoun
- Function : Author
- PersonId : 988949
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.