Interleukin 33 Critically Regulates Angiogenesis and Inflammation in Large Vessels Vasculitis

Anne-Claire Desbois¹, Aurélie LEROYER², Marlène Garrido³, Julien Gaudric⁴, Cloé Comarmond⁵, David Klatzman⁶, Philippe Cluzel⁷, Pierre Fouret⁸, Laurent Chiche⁹, Fabien Koskas¹⁰, Gilles Kaplanski¹¹, Patrice Cacoub¹² and David Saadoun¹³, ¹Hôpital Pitié-Salpêtrière, Internal Medicine and Clinical Immunology, Paris, France, ²Faculté de Pharmacie, Marseille, France, ³I3 laboratory, Pitié-Salpétrière, Paris, France, ⁴Department of Vascular surgery GHPS, Paris, France, ⁵DHU 2iB Internal Medicine Referal Center for Autoimmune diseases Pitie Hospital, Paris, France, ⁶UPMC Université Paris 06, UMR 7211, Paris, France, ⁷Cadiovascular Imaging and Interventional Radiology, Pitié-Salpétrière, Paris, France, ⁸Hôpital La Pitié Salpétrière, Paris, France, ⁹Service de Chirurgie Vasculaire, Groupe Hospitalier Pitié-Salpêtrière, Paris, France, ¹⁰Department of Internal Medicine and 2Laboratory I3 « Immunology, Immunopathology, Immunotherapy », UMR CNRS 7211, INSERM U959, Groupe Hospitalier Pitié-Salpetrière, Université Pierre et Marie Curie, Paris 6, Paris, France, Paris, France, ¹¹Aix-Marseille Université - Internal Medicine hopital conception - F-13000 Marseilles, Marseille, France, ¹²Internal Medicine Department, University Hospital “Pitié-Salpêtrière”, “Pierre et Marie Curie Paris VI” University, Paris, France, ¹³Department of Internal Medicine and clinical Immunology. French National Reference Center for Autoimmune Diseases. DHU I2B (Inflammation, Immunotherapy and Biotherapy), UPMC, Paris VI, Hôpital Pitié Salpétrière, AP-HP, UPMC, Univ Paris 06, Paris, France

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Angiogenesis, Immune regulation, interleukins (IL) and vasculitis

Session Information

Date: Sunday, November 13, 2016

Title: Vasculitis - Poster I: Large Vessel Vasculitis and Polymyalgia Rheumatica

Session Type: ACR Poster Session A

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

Background/Purpose: Large vessels vasculitis (LVV) include Takayasu disease (TD) and Giant Cell Arteritis (GCA). Interleukin 33 (IL-33) is a cytokine which controls immune responses and has also an important vascular impact. We aimed to analyse the role of IL-33 and its receptor ST2 in the pathogenesis of LVV.

Methods: TD and GCA patients fulfilling the ACR criteria, with active or inactive disease and age-matched controls (HD) were included. We performed quantitative measurement of IL-33 in sera by ELISA, analysis of cytokine production by flow cytometry and Luminex. Immunohistochemical analysis of inflamed aorta and temporal arteries from TD and GCA patients was also performed.

Results: IL-33 and soluble ST2 were overexpressed in sera of LVV patients as compared to age-matched controls (p=0.03 in TD and p=0.013 in GCA for IL-33 and p=0.0002 in GCA for ST2). By immunofluorescence in inflamed vessels, we found endothelial IL-33 expression pattern mainly in the adventice together with the expression of its receptor ST2 restricted to inflammatory infiltrate. In both diseases, we highlighted in the vascular inflammatory lesions, the expression of Th2 cytokines (IL4) and of IL10. We have shown that IL-33 induced an increase of CD4+ T cells secreting IL-4 after 3 and 5 days of culture in GCA patients (p=0.01). In both disease, we have found that IL-33 led to an increased IL-5 and IL-13 secretion in the supernatants of mononuclear cell cultures. Besides anti-inflammatory properties of IL-33 in LVV, we demonstrated in mice that IL-33 led to an increased vascular permeability in both diseases (p=0.004). As mast cells represent one of the main targets of IL-33, we have repeated a Miles assay in mice KO for mast cells. Vascular permeability was significantly decreased in KO mice injected with the same TA patients as compared to WT mice (p=0.007). In vitro, the exposure of TA sera to HUVECS led to the increase of VeCad phosphorylation compared to controls sera (p=0.03). Sera from TD patients also significantly increased the migration of endothelial cells whereas the exposure of serum to anti-IL-33 significantly decreased the number of transmigrated cells.

Conclusion: These findings open new perspectives for the role of IL-33 in the pathogenesis of LVV. IL-33 may regulate the inflammatory immune response by promoting Th2-polarization and increases vascular permeability, though mast cells.

Disclosure: A. C. Desbois, None; A. LEROYER, None; M. Garrido, None; J. Gaudric, None; C. Comarmond, None; D. Klatzman, None; P. Cluzel, None; P. Fouret, None; L. Chiche, None; F. Koskas, None; G. Kaplanski, None; P. Cacoub, None; D. Saadoun, None.

To cite this abstract in AMA style:

Desbois AC, LEROYER A, Garrido M, Gaudric J, Comarmond C, Klatzman D, Cluzel P, Fouret P, Chiche L, Koskas F, Kaplanski G, Cacoub P, Saadoun D. Interleukin 33 Critically Regulates Angiogenesis and Inflammation in Large Vessels Vasculitis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/interleukin-33-critically-regulates-angiogenesis-and-inflammation-in-large-vessels-vasculitis/. Accessed .

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