Date: Sunday, November 5, 2017
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Large vessel vasculitis (LVV) include Takayasu arteritis (TA) and giant cell arteritis (GCA). Arterial lesions in LVV result from chronic inflammation and neoangiogenesis. IL-33, a cytokine involved in angiogenesis and vascular permeability has been previously found overexpressed in arteries of large vessel vasculitis. We aimed at assessing its effects on the regulation of immune response and angiogenesis.
In vitro studies on angiogenesis were performed by using human endothelial cells to assess migration, proliferation and angiogenesis. Vascular permeability was assessed in vivo, using Miles assay. The effects of IL-33 on immune response were determined by assessing the production of cytokines by Multiplex in cultures of peripheral mononuclear cells (PBMC) with or without IL-33 stimulation and the proportion of regulatory T cells in cultures of mast cells and CD4+ T cells with or without IL-33 stimulation.
We identified increased IL-33 levels in serum and in inflammatory lesions of TA and GCA patients as compared to controls. Sera from TA patients have angiogenic properties by promoting HUVECs proliferation, tube and sprout formation and were also able to induce vessel permeability in vivo. The addition of neutralizing anti-IL-33 antibody inhibits neoangiogenesis, migration of endothelial cells in vitro and vascular permeability in vivo. As mast cells are one of the main targets of IL-33, we repeated these experiments in mast-cells deficient mice in which in vivo effects were abolished. Significant increased number of mast cells was observed in aorta lesions of both diseases as compared to non-inflammatory aorta controls. IL-33 overexpression was accompanied by an increased expression of Th2-related cytokines by enhancing the secretion of IL-5 and IL-4. IL-33 also promoted the regulatory immune response by increasing the proportion of regulatory T (Tregs) cells. Consistently, IL-33 and mast cells dramatically increased the proportion of Tregs and the activity of indoleamine 2 3-dioxygenase (IDO).
IL-33/ST2 axis, through its interaction with mast cells, has a critical role in the pathogenesis of LVV.
To cite this abstract in AMA style:Desbois AC, Cacoub P, LEROYER A, Tellier E, Garrido M, Maciejewski-Duval A, Comarmond C, Barete S, Arock M, Bruneval P, Launay JM, Fouret P, Blank U, Rosenzwajg M, Klatzman D, Jarraya M, Cluzel P, Koskas F, Kaplanski G, Saadoun D. The Critical Role of Interleukin-33 in Promoting Angiogenesis and Regulates Inflammation through Mast Cells in Takayasu Arteritis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/the-critical-role-of-interleukin-33-in-promoting-angiogenesis-and-regulates-inflammation-through-mast-cells-in-takayasu-arteritis/. Accessed May 30, 2020.
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