The Critical Role of Interleukin-33 in Promoting Angiogenesis and Regulates Inflammation through Mast Cells in Takayasu Arteritis

Anne-Claire Desbois¹, Patrice Cacoub², Aurélie LEROYER³, Edwige Tellier⁴, Marlène Garrido⁵, Anna Maciejewski-Duval⁶, Cloé Comarmond⁷, Stéphane Barete⁶, Michel Arock⁶, Patrick Bruneval⁸, Jean-Marie Launay⁹, Pierre Fouret¹⁰, Ulrich Blank¹¹, Michelle Rosenzwajg⁶, David Klatzman¹², Mohamed Jarraya¹³, Philippe Cluzel¹⁴, Fabien Koskas¹⁵, Gilles Kaplanski¹⁶ and David Saadoun¹⁷, ¹Hôpital Pitié-Salpêtrière, Internal Medicine and Clinical Immunology, Paris, France, ²Department of Internal Medicine and Clinical Immunology, Groupe Hospitalier Pitié-Salpêtrière, Paris, France, ³Faculté de Pharmacie, Marseille, France, ⁴Université Marseille, Marseille, France, ⁵I3 laboratory, Pitié-Salpétrière, Paris, France, ⁶GHPS, Paris, France, ⁷DHU 2iB Internal Medicine Referal Center for Autoimmune diseases Pitie Hospital, Paris, France, ⁸HEGP, Paris, France, ⁹Hôpital lariboisière, Paris, France, ¹⁰Hôpital La Pitié Salpétrière, Paris, France, ¹¹Hôpital Bichat, Paris, France, ¹²UPMC Université Paris 06, UMR 7211, Paris, France, ¹³Hôpital Saint Louis, Paris, France, ¹⁴Department of cardiovascular imagery, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Pitié Salpétrière, 83 Boulevard de l'Hôpital, 75013, Paris, France., Paris, France, ¹⁵Department of vascular surgery, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France, ¹⁶Aix-Marseille Université - Internal Medicine hopital conception - F-13000 Marseilles, Marseille, France, ¹⁷Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), F-75005, Paris, France; INSERM, UMR_S 959, F-75013, Paris, France; CNRS, FRE3632, F-75005, Paris, France; AP-HP, Groupe Hospitalier, Paris, France

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Angiogenesis, cytokines, Regulatory cells, takayasu arteritis and vasculitis

Session Information

Date: Sunday, November 5, 2017

Title: Cytokines, Mediators, Cell-Cell Adhesion, Cell Trafficking and Angiogenesis Poster I: The Variable World of Intercellular Signalling

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose:

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.

Methods:

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.

Results:

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).

Conclusion:

IL-33/ST2 axis, through its interaction with mast cells, has a critical role in the pathogenesis of LVV.

Disclosure: A. C. Desbois, None; P. Cacoub, None; A. LEROYER, None; E. Tellier, None; M. Garrido, None; A. Maciejewski-Duval, None; C. Comarmond, None; S. Barete, None; M. Arock, None; P. Bruneval, None; J. M. Launay, None; P. Fouret, None; U. Blank, None; M. Rosenzwajg, None; D. Klatzman, None; M. Jarraya, None; P. Cluzel, None; F. Koskas, None; G. Kaplanski, None; D. Saadoun, None.

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 .

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