Alessandro Zerbini1, Francesco Muratore2, Luigi Boiardi3, Francesco Ciccia4, Martina Bonacini1, Lucia Belloni1, Alberto Cavazza5, Luca Cimino6, Antonio Moramarco6, Riccardo Alessandro7, Aroldo Rizzo8, Maria Parmeggiani1, Carlo Salvarani2, Stefania Croci1. 1. Unit of Clinical Immunology, Allergy and Advanced Biotechnologies, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia. 2. Department of Surgery, Medicine, Dentistry and Morphological Sciences with interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena. 3. Unit of Rheumatology, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia. 4. Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia, Università degli Studi di Palermo, Palermo. 5. Unit of Pathology. 6. Unit of Ophthalmology, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia. 7. Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università degli studi di Palermo. 8. Dipartimento di Oncoematologia, Sezione di Anatomia Patologica, Azienda Ospedaliera Ospedali riuniti Villa Sofia Cervello, Palermo, Italy.
Abstract
Objectives: GCA is characterized by arterial remodelling driven by inflammation. IL-22 is an attractive cytokine which acts at the crosstalk between immune and stromal cells. We hypothesized that IL-22 might be induced in GCA and might be involved in disease pathogenesis. Methods: Patients subjected to temporal artery biopsies (TABs) naïve from therapy were enrolled: 27 biopsy-proven GCA, 8 biopsy-negative GCA, 21 biopsy-negative non-GCA patients. Expression of IL-22 was determined in TABs by immunohystochemistry, in plasma by ELISA, in peripheral blood mononuclear cells by real-time PCR and flow cytometry. Effects of IL-22 on viability and gene expression of primary cultures obtained from TABs were also evaluated. Results: Inflamed TABs from GCA patients showed a higher expression of IL-22 and IL-22 specific receptor subunit (IL-22R1) than non-inflamed TABs. IL-22 was expressed in infiltrating immune cells and spindle shaped cells, IL-22R1 was expressed in endothelial cells. Patients with biopsy-proven GCA showed increased levels of IL-22 in plasma than patients with biopsy-negative GCA, without GCA and healthy subjects. Peripheral blood mononuclear cells from GCA patients expressed higher IL-22 transcript than healthy subjects. After stimulation in vitro with phorbol 12-myristate 13-acetate and ionomycin, the frequencies of Th22 and IL-22+ CD4+ lymphocytes were similar between patients with and without GCA. Treatment with IL-22 of primary cultures obtained from TABs increased cell viability under stress conditions and expression of B-cell activating factor. Conclusion: IL-22 is increased in patients with GCA and affects viability and gene expression of arterial cells, supporting a potential role in disease pathogenesis.
Objectives: GCA is characterized by arterial remodelling driven by inflammation. IL-22 is an attractive cytokine which acts at the crosstalk between immune and stromal cells. We hypothesized that IL-22 might be induced in GCA and might be involved in disease pathogenesis. Methods: Patients subjected to temporal artery biopsies (TABs) naïve from therapy were enrolled: 27 biopsy-proven GCA, 8 biopsy-negative GCA, 21 biopsy-negative non-GCA patients. Expression of IL-22 was determined in TABs by immunohystochemistry, in plasma by ELISA, in peripheral blood mononuclear cells by real-time PCR and flow cytometry. Effects of IL-22 on viability and gene expression of primary cultures obtained from TABs were also evaluated. Results: Inflamed TABs from GCA patients showed a higher expression of IL-22 and IL-22 specific receptor subunit (IL-22R1) than non-inflamed TABs. IL-22 was expressed in infiltrating immune cells and spindle shaped cells, IL-22R1 was expressed in endothelial cells. Patients with biopsy-proven GCA showed increased levels of IL-22 in plasma than patients with biopsy-negative GCA, without GCA and healthy subjects. Peripheral blood mononuclear cells from GCA patients expressed higher IL-22 transcript than healthy subjects. After stimulation in vitro with phorbol 12-myristate 13-acetate and ionomycin, the frequencies of Th22 and IL-22+ CD4+ lymphocytes were similar between patients with and without GCA. Treatment with IL-22 of primary cultures obtained from TABs increased cell viability under stress conditions and expression of B-cell activating factor. Conclusion: IL-22 is increased in patients with GCA and affects viability and gene expression of arterial cells, supporting a potential role in disease pathogenesis.
Authors: Dan Pugh; Maira Karabayas; Neil Basu; Maria C Cid; Ruchika Goel; Carl S Goodyear; Peter C Grayson; Stephen P McAdoo; Justin C Mason; Catherine Owen; Cornelia M Weyand; Taryn Youngstein; Neeraj Dhaun Journal: Nat Rev Dis Primers Date: 2022-01-06 Impact factor: 65.038