Abstract
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. 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. 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. IL-22 is increased in patients with GCA and affects viability and gene expression of arterial cells, supporting a potential role in disease pathogenesis.
Highlights
Giant cell arteritis (GCA) is the most common vasculitis in western countries in individuals older than 50 years of age
Inflamed temporal artery biopsies (TABs) from GCA patients showed a higher expression of IL-22 and IL-22 specific receptor subunit (IL-22R1) than non-inflamed TABs
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
Summary
Giant cell arteritis (GCA) is the most common vasculitis in western countries in individuals older than 50 years of age It is a chronic inflammatory disease affecting large and medium-sized arteries, especially the branches of the proximal aorta [1, 2]. IL-22 has been reported to regulate the crosstalk between cells of the immune system and tissue-resident cells, at barrier surfaces (e.g. respiratory, gastrointestinal systems and skin) [6, 7]. It has immunomodulator properties in infection, inflammation, autoimmunity, cancer, tissue regeneration and host defence. IL-22 might have a role in arterial remodelling, because it regulates the intercommunication between the immune system and stromal cells
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