Th1 and Th17 Cytokines Drive Takayasu Arteritis Inflammation

David Saadoun¹, Marlène Garrido², Cloé Comarmond³, Anne-Claire Desbois⁴, Fanny Domont⁴, Léa Savey⁵, Benjamin Terrier⁶, Michelle Rosenzwajg⁷, David Klatzman⁸, Pierre Fourret⁹, Philippe Cluzel¹⁰, Laurent Chiche¹¹, Julien Gaudric¹², Fabien Koskas¹³ and Patrice Cacoub¹⁴, ¹DHU 2iB Internal Medicine Referal Center for Autoimmune diseases Pitie Hospital, Paris, France, ²Internal medicine and clinical immunology, UMR 7211, INSERM U959, Hôpital Pitié-Salpêtrière, Paris, France, ³Internal Medicine and Clinical Imunology, Referal Center for Autoimmune diseases, Internal Medicine and Clinical Imunology, Hôpital Pitié Salpétrière, Paris, France, ⁴Hôpital Pitié-Salpêtrière, Internal Medicine and Clinical Immunology, Paris, France, ⁵Hôpital Pitié-Salpêtrière, Internal Medicine and Clinical Immunology, P, France, ⁶National Referral Center for Rare Systemic Autoimmune Diseases, Cochin Hospital, Paris, France, ⁷UMR 7211, INSERM U959, Hôpital Pitié-Salpêtrière, Paris, France, ⁸UPMC Université Paris 06, UMR 7211, Paris, France, ⁹Hôpital Pitié-Salpêtrière, Anathomopathology, Paris, France, ¹⁰Vascular and Interventional Imaging Department, Paris, France, ¹¹Vascular Surgery, Paris, France, ¹²Department of Vascular surgery GHPS, Paris, France, ¹³Vascular Surgery, Assistance Publique-Hôpitaux de Paris, Hopital Pitié-Salpétrière, Paris, France, ¹⁴Groupe Hospitalier Pitié Salpétrière, Service de Médecine Interne, DHU i2B, Paris, France

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: T cells and takayasu arteritis

Session Information

Title: T cell Biology in Lupus, Vasculitis, Myositis and Other Autoimmunity

Session Type: Abstract Submissions (ACR)

Background/Purpose: Takayasu arteritis (TA) is a large-vessel vasculitis inducing damage of the aorta and its branches. Glucocorticoids remain the gold standard of therapy in TA. However, the nature of T cell driving vascular inflammation and the effects of glucocorticoids on the systemic components of TA are not understood.

Methods: T cell homeostasis and cytokines production were analyzed in peripheral blood and aorta inflammatory lesions using Luminex, flow cytometry, and immunohistochemistry analysis. The study included 41 TA patients fulfilling the ACR criteria [17 active (aTA) and 24 in remission (rTA)], 30 giant cell arteritis (GCA) patients (disease control) and 20 age and sex-matched controls.

Results:

We first demonstrated the promotion of Th1 and Th17 responses that correlates with TA activity. We determined whether serum from TA patients was able to modulate T cell differentiation in healthy controls. The addition of serum from active TA patients in sorted CD4⁺ T cells culture of healthy donors induced a significant production of IFN-g and IL-17A. We demonstrated the the strong expression of IFN-g, and IL-6 producing T cells within vascular inflammatory infiltrates of TA. Glucocorticoid therapy were associated to decreased circulating Th1 cytokines with significantly lower IL-2 (mean±SEM; 2812±690.1 vs. 7228±1536 pg/ml, p=0.0196), IFN-g (1437±367.3 vs. 7124±1818pg/ml, p=0.0019) and TNF-a (643.3±106.4 vs. 1438±196.6pg/ml, p=0.01) in steroid treated TA compared to steroid free TA patients, respectively. However, glucocorticoids essentially left unaffected Th17 cytokines (i.e. IL-1b, IL-6, IL-17 and IL-23).

Conclusion: Our data provided the first evidence that Th1 and Th17 immunity seems to be important in driving TA inflammation, both systemically and in the blood vessels. In addition, only one of these pathways was amendable to glucocorticoid-mediated suppression. Glucocorticoids are associated to decrease Th1 cytokines and spared Th17 cytokines in TA.

Disclosure:

D. Saadoun,
None;

M. Garrido,
None;

C. Comarmond,
None;

A. C. Desbois,
None;

F. Domont,
None;

L. Savey,
None;

B. Terrier,
None;

M. Rosenzwajg,
None;

D. Klatzman,
None;

P. Fourret,
None;

P. Cluzel,
None;

L. Chiche,
None;

J. Gaudric,
None;

F. Koskas,
None;

P. Cacoub,

Astra Zeneca, Bayer, Boehringer Ingelheim, Gilead, Glaxo Smith Kline, Janssen, Merck Sharp Dohme, Roche, Servier, Vifor.,

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