Senescent cells in giant cell arteritis display an inflammatory phenotype participating in tissue injury via IL-6-dependent pathways.

Autor:	Veroutis D; Molecular Carcinogenesis Group, Department of Histology and Embryology, Medical School, National and Kapodistrian University of Athens, Athens, Greece., Argyropoulou OD; Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece., Goules AV; Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.; Research Institute for Systemic Autoimmune Diseases, Athens, Greece.; Joint Rheumatology Program, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece., Kambas K; Laboratory of Molecular Genetics, Department of Immunology, Hellenic Pasteur Institute, Athens, Greece., Palamidas DA; Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.; Research Institute for Systemic Autoimmune Diseases, Athens, Greece., Evangelou K; Molecular Carcinogenesis Group, Department of Histology and Embryology, Medical School, National and Kapodistrian University of Athens, Athens, Greece., Havaki S; Molecular Carcinogenesis Group, Department of Histology and Embryology, Medical School, National and Kapodistrian University of Athens, Athens, Greece., Polyzou A; Molecular Carcinogenesis Group, Department of Histology and Embryology, Medical School, National and Kapodistrian University of Athens, Athens, Greece., Valakos D; Center of Basic Research, Biomedical Research Foundation Academy of Athens, Athens, Greece., Xingi E; Light Microscopy Unit, Hellenic Pasteur Institute, Athens, Greece., Karatza E; Second Propaedeutic Department of Surgery, Laikon General Hospital, Athens, Greece., Boki KA; Rheumatology Unit, Sismanoglion Hospital, Athens, Greece., Cavazza A; Unit of Pathology, Azienda Unità Sanitaria Locale-IRCCS, Reggio Emilia, Italy., Kittas C; Molecular Carcinogenesis Group, Department of Histology and Embryology, Medical School, National and Kapodistrian University of Athens, Athens, Greece., Thanos D; Center of Basic Research, Biomedical Research Foundation Academy of Athens, Athens, Greece., Ricordi C; Unit of Rheumatology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, and University of Modena, Reggio Emilia, Italy.; Department of Surgery, Medicine, Dentistry and Morphological Sciences with interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy., Marvisi C; Unit of Rheumatology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, and University of Modena, Reggio Emilia, Italy.; Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy., Muratore F; Unit of Rheumatology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, and University of Modena, Reggio Emilia, Italy.; Department of Surgery, Medicine, Dentistry and Morphological Sciences with interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy., Galli E; Unit of Rheumatology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, and University of Modena, Reggio Emilia, Italy.; Department of Surgery, Medicine, Dentistry and Morphological Sciences with interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy., Croci S; Unit of Clinical Immunology, Allergy and Advanced Biotechnologies, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy., Salvarani C; Unit of Rheumatology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, and University of Modena, Reggio Emilia, Italy agtzi@med.uoa.gr vgorg@med.uoa.gr carlo.salvarani@ausl.re.it.; Department of Surgery, Medicine, Dentistry and Morphological Sciences with interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy., Gorgoulis VG; Molecular Carcinogenesis Group, Department of Histology and Embryology, Medical School, National and Kapodistrian University of Athens, Athens, Greece agtzi@med.uoa.gr vgorg@med.uoa.gr carlo.salvarani@ausl.re.it.; Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.; Molecular and Clinical Cancer Sciences, Manchester Cancer Research Centre, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK.; Biomedical Research Foundation, Academy of Athens, Athens, Greece., Tzioufas AG; Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece agtzi@med.uoa.gr vgorg@med.uoa.gr carlo.salvarani@ausl.re.it.; Research Institute for Systemic Autoimmune Diseases, Athens, Greece.; Joint Rheumatology Program, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.; Center of stratified medicine in autoimmune and rheumatic diseases, Biomedical Research Foundation Academy of Athens, Athens, Greece.
Jazyk:	angličtina
Zdroj:	Annals of the rheumatic diseases [Ann Rheum Dis] 2024 Feb 15; Vol. 83 (3), pp. 342-350. Date of Electronic Publication: 2024 Feb 15.
DOI:	10.1136/ard-2023-224467
Abstrakt:	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. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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