Date: Monday, November 6, 2017
Session Title: T Cell Biology and Targets in Autoimmune Disease Poster I
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: mTORC1 drives the proinflammatory expansion of T helper (TH) type 1, TH17 cells and controls fibroblast proliferation, typical features of Takayasu arteritis (TA) pathogenesis. Molecular pathways involved in arterial lesions of TA are unknown.
Methods: We evaluate pathway activation in the mammalian target of rapamycin complex (mTORC) and the nature of cell proliferation in the vessels of patients with TA by using double immunostaining, western blot and flow cytometry.
Results: Proliferation of both endothelial cells and vascular smooth-muscle cells was shown in vascular lesions in TA. The vascular endothelium of proliferating aorta vessel from patients with TA showed indications of activation of the mTORC1 pathway. In cultured vascular endothelial cells, sera from patients with TA stimulated mTORC1 through the phosphatidylinositol 3-kinase (PI3K)–AKT pathway. Activation of mTORC was also found in Th1 and Th17 cells both systemically and in the blood vessels. Patients with TA exhibited a diminished AKT phosphorylation in Tregs. Inhibition of mTOR pathway with rapamycin increase Treg and decrease CD4+IFN+, CD4+IL17+ and CD4+IL21+ cells in patients with TA.
Conclusion: Our results suggest that the mTORC pathway is involved in the vascular lesions of Takayasu arteritis. Rapamycin could restore T cells homeostasis in patients with TA.
To cite this abstract in AMA style:Comarmond C, Leroyer A, Mohamad Z, Fourez JP, Koskas F, Cluzel P, Maciejewski-Duval A, Garrido M, Cacoub P, Saadoun D. mTOR Pathway Activation in Takayasu Arteriti [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/mtor-pathway-activation-in-takayasu-arteriti/. Accessed January 27, 2022.
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