Novel immune cell phenotypes in spondyloarthritis pathogenesis

Abstract

Spondyloarthritis (SpA) is a heterogeneous group of chronic inflammatory diseases of unknown etiology. Over time, the plethora of cellular elements involved in its pathogenesis has progressively enriched together with the definition of specific cytokine pathways. Recent evidence suggests the involvement of new cellular mediators of inflammation in the pathogenesis of SpA or new subgroups of known cellular mediators. The research in this sense is ongoing, and it is clear that this challenge aimed at identifying new cellular actors involved in the perpetuation of the inflammatory process in AxSpA is not a mere academic exercise but rather aims to define a clear cellular hierarchy. Such a definition could pave the way for new targeted therapies, which could interfere with the inflammatory process and specific pathways that trigger immune system dysregulation and stromal cell activity, ultimately leading to significant control of the inflammation and new bone formation in a significant number of patients. In this review, we will describe the recent advances in terms of new cellular actors involved in the pathogenesis of SpA, focusing our attention on stromal cells and innate and adaptive immunity cells.

Intestinal Microbial Metabolites in Ankylosing Spondylitis

“…Human studies in SpA and animal models demonstrated T cells’ participation in the pathogenesis of both articular and extraarticular manifestations of AS [ 13 , 81 ].…”

“…This increase could be considered an attempt to counteract the inflammation associated to SpA [ 82 ]. Conversely, in HLA-B27/β2m transgenic rat altered ratio between IL-17/IL-10 has been observed, which partially depends on a defective IL-10 production from Tregs [ 13 , 83 ]. In the same animal models, SCFAs seems to be paradoxically increased rather than decreased, suggesting a possible anti-inflammatory response.…”

“…Riboflavin metabolites appear to elicit MR1-dependent activation of MAIT cells, while 6-formyl pterin, a vitamin B9 intermediate, does not appear to have any stimulating effect [ 98 ]. This microbiota-induced activation of MAIT cells may have notable implications in the pathogenesis of AS [ 13 ]. It is worth noting that, in humans, the primary localization of MAIT cells are the mucosal surfaces, but they are particularly abundant also in the liver and in circulation, where they represent 45% and 10% of total T cells, respectively, and represent one of the most abundant sources of IL-17 [ 99 ].…”

“…Intestinal inflammation seems invariably linked to the dysfunction of the epithelial gut barrier, leading to a condition named “leaky gut” [ 8 , 10 , 11 ]. The inefficient separation of the intestinal lumen with the subepithelial space is associated with the aberrant activation of mucosal resident immune cells that, recirculating, may transfer the inflammation to the joint, establishing a pathogenic gut-joint axis [ 12 , 13 , 14 , 15 ]. The mucosal barrier alteration is part of a vicious circle involving the genetic predisposition, particularly HLA-B27, environmental factors, and altered intestinal dysbiosis [ 9 , 16 ].…”

Recent advances in spondyloarthritis: positive developments in the seronegative domain

“…This may set the stage for disruption of CTL homeostasis reflected in a failure to drive these cells into an exhausted phenotype. But the dramatis personae in this play certainly involves a cast of characters well beyond CD8+ and CD4+ T lymphocytes [9]. This includes mesenchymal stromal cells, fibroblast-like synoviocytes, type 3 innate lymphoid cells, MAIT cells and iNK T cells.…”