Differential expression of interleukin‐17 family cytokines in intact and complicated human atherosclerotic plaques

Abstract

In addition to the classical TH1 and TH2 cytokines, members of the recently identified IL-17 cytokine family play an important role in regulating cellular and humoral immune responses. At present nothing is known about the role of these cytokines in atherosclerosis. Expression of IL-17A, -E and -F was investigated in atherosclerotic tissue by rtPCR and immunohistochemistry. IL-17E and its receptor were further studied in cultured smooth muscle cells and endothelial cells, using rtPCR and western blot. rtPCR showed that IL-17A, -E and -F were expressed in the majority of plaques under investigation. IL-17A/F was expressed by mast cells in all stages of plaque development. IL-17A/F(+) neutrophils were always observed in complicated plaques, but hardly in intact lesions. IL-17A/F(+) Tcells ('TH17') were never observed. IL-17E was expressed by smooth muscle cells and endothelial cells in both normal and atherosclerotic arteries, and in advanced plaques also extensively by mature B cells. Cultured smooth muscle cells and endothelial cells were found to express both IL-17E and its functional receptor (IL-17RB). The constitutive expression of IL-17E by resident plaque cells, and the additional presence of IL-17E(+) B cells and IL-17A/F(+) neutrophils in advanced and complicated plaques indicates a complex contribution of IL-17 family cytokines in human atherosclerosis, depending on the stage and activity of the disease.

Interleukin‐17–positive mast cells contribute to synovial inflammation in spondylarthritis

“…First, as in previous studies (18,43,44), we used a polyclonal goat antibody to IL-17A that can also cross-react, to a certain degree, with IL-17F. Even though the ELISA used for the ex vivo biopsy experiments was specific for IL-17A, and previous in vitro experiments have demonstrated the production of IL-17A by human mast cells (18), it still remains to be formally demonstrated which IL-17 isotype is produced by mast cells in the synovial tissue.…”

“…Interestingly, the production and secretion of cytokines are regulated in a manner different from the degranulation function (40)(41)(42). Based on the recent description of IL-17 production by mast cells in inflammatory diseases (19,43,44) and considering the emerging role of IL-17 in SpA (30), we focused on the expression and production of IL-17 by mast cells in SpA synovitis. Our results confirmed not only that synovial mast cells express IL-17, but also that both the absolute number of mast cells and the proportion of synovial mast cells expressing IL-17 is significantly increased in SpA synovitis when compared to RA synovitis.…”

The Aryl Hydrocarbon Receptor Modulates Acute and Late Mast Cell Responses

“…The consequences of this event could be now evaluated in diseases where MCs represent a potent source of proinflammatory cytokines and exposure to AhR ligands is likely to occur (38). For instance, MCs alone or together with other non-T immune cells are predominant IL-17 + cells in psoriatic lesions in human skin (25), in atherosclerotic plaques (39), as well as in rheumatoid arthritis, osteoarthritis, and spondyloarthritis synovium (24,26,40). Human MCs require the Th17 lineage-defining transcription factor Rorc to produce IL-17 in response to different stimuli (24).…”

Th17 and non-Th17 interleukin-17-expressing cells in chronic lymphocytic leukemia: delineation, distribution, and clinical relevance

“…Expression of IL-17A in cells of the granulopoietic pathway has not been reported in human cancers, although such cells were found in human atheromatous plaques. 7 It has been reported that myeloid-derived suppressor cells can express IL-17 and promote tumor development in a murine hepatocarcinoma model. 39 Because all CLL spleens had higher numbers of immature myeloid cells than spleens from healthy individuals, a previously unrecognized splenic granulopoiesis may occur in CLL.…”

“…6 IL-17 is produced by Th17 cells and other cells: CD8 + T cells, γδ T cells, invariant NKT cells, mast cells, and granulocytes. 7 IL-17 has pleiotropic functions and multiple targets, mostly explored in mouse models and increasingly linked to human diseases. [8][9][10][11] Generation of human Th17 cells from naïve precursors is co-promoted by IL-6 and IL-1β and expansion of human Th17 cells is maintained by IL-23; 9 a role for transforming growth factor-β (TGF β) in human Th17-cell differentiation is controversial.…”