Senescent cells in giant cell arteritis display an inflammatory phenotype participating in tissue injury via IL-6-dependent pathways
Authors
Veroutis, DArgyropoulou, OD
Goules, AV
Kambas, K
Palamidas, DA
Evangelou, K
Havaki, S
Polyzou, A
Valakos, D
Xingi, E
Karatza, E
Boki, KA
Cavazza, A
Kittas, C
Thanos, D
Ricordi, C
Marvisi, C
Muratore, F
Galli, E
Croci, S
Salvarani, C
Gorgoulis, Vassillis G
Tzioufas, AG
Affiliation
Molecular and Clinical Cancer Sciences, Manchester Cancer Research Centre, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.Issue Date
2023
Metadata
Show full item recordAbstract
OBJECTIVES: Age is the strongest risk factor of giant cell arteritis (GCA), implying a possible pathogenetic role of cellular senescence. To address this question, we applied an established senescence specific multimarker algorithm in temporal artery biopsies (TABs) of GCA patients. METHODS: 75(+) TABs from GCA patients, 22(-) TABs from polymyalgia rheumatica (PMR) patients and 10(-) TABs from non-GCA/non-PMR patients were retrospectively retrieved and analysed. Synovial tissue specimens from patients with inflammatory arthritis and aorta tissue were used as disease control samples. Senescent cells and their histological origin were identified with specific cellular markers; IL-6 and MMP-9 were investigated as components of the senescent associated secretory phenotype by triple costaining. GCA or PMR artery culture supernatants were applied to fibroblasts, HUVECs and monocytes with or without IL-6R blocking agent to explore the induction of IL-6-associated cellular senescence. RESULTS: Senescent cells were present in GCA arteries at higher proportion compared with PMR (9.50% vs 2.66%, respectively, p<0.0001) and were mainly originated from fibroblasts, macrophages and endothelial cells. IL-6 was expressed by senescent fibroblasts, and macrophages while MMP-9 by senescent fibroblasts only. IL-6(+) senescent cells were associated with the extension of vascular inflammation (transmural inflammation vs adventitia limited disease: 10.02% vs 4.37%, respectively, p<0.0001). GCA but not PMR artery culture supernatant could induce IL-6-associated senescence that was partially inhibited by IL-6R blockade. CONCLUSIONS: Senescent cells with inflammatory phenotype are present in GCA arteries and are associated with the tissue inflammatory bulk, suggesting a potential implication in disease pathogenesis.Citation
Veroutis D, Argyropoulou OD, Goules AV, Kambas K, Palamidas DA, Evangelou K, et al. Senescent cells in giant cell arteritis display an inflammatory phenotype participating in tissue injury via IL-6-dependent pathways. Annals of the rheumatic diseases. 2023 Nov 24. PubMed PMID: 38050005. Epub 2023/12/05. eng.Journal
Annals of the Rheumatic DiseasesDOI
10.1136/ard-2023-224467PubMed ID
38050005Additional Links
https://dx.doi.org/10.1136/ard-2023-224467Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1136/ard-2023-224467
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