Abstract
Spondyloarthritis (SpA) is a chronic inflammatory rheumatism characterized by inflammation of sacroiliac joints, peripheral joints, and spine. The Assessment of SpondyloArthritis Society describes three disease forms: axial (axSpA), peripheral, and enthesitic SpA. Each may be associated with extra-articular manifestations: psoriasis, inflammatory bowel disease, and acute anterior uveitis. Genome-wide association studies performed in axSpA and psoriatic arthritis (PsA) have shown a shared genetic background, especially the interleukin 23 (IL-23)/IL-17 pathway, which suggests pathophysiological similarities. The convincing positive results of clinical trials assessing the effect of secukinumab and ixekizumab (anti-IL-17A monoclonal antibodies) in axSpA and PsA have reinforced the speculated crucial role of IL-17 in SpA. Nevertheless, and obviously unexpectedly, the differential efficacy of anti-IL-23–targeted treatments between axSpA (failure) and PsA (success) has profoundly disrupted our presumed knowledge of disease pathogeny. The cells able to secrete IL-17, their dependence on IL-23, and their respective role according to the clinical form of the disease is at the heart of the current debate to potentially explain these observed differences in efficacy of IL-23/IL-17–targeted therapy. In fact, IL-17 secretion is usually mainly related to T helper 17 lymphocytes. Nevertheless, several innate immune cells express IL-23 receptor and can produce IL-17. To what extent these alternative cell populations can produce IL-17 independent of IL-23 and their respective involvement in axSpA and PsA are the crucial scientific questions in SpA. From this viewpoint, this is a nice example of a reverse path from bedside to bench, in which the results of therapeutic trials allow for reflecting more in depth on the pathophysiology of a disease. Here we provide an overview of each innate immunity-producing IL-17 cell subset and their respective role in disease pathogeny at the current level of our knowledge.
Highlights
Spondyloarthritis (SpA) is a chronic inflammatory disease characterized by inflammation of the sacroiliac joints, peripheral joints, and spine
We have described the different IL-17–producing cells belonging to the innate immunity compartment
They have dual IL-17 production capacity that could be of prime importance in SpA pathogenesis. Their ability to secrete IL-17 is immediate, not requiring differentiation or proliferation steps. They are at the ultimate stage of maturation and ready to “draw.” as for other cells belonging to the innate immunity, their migratory capacity is pronounced
Summary
Spondyloarthritis (SpA) is a chronic inflammatory disease characterized by inflammation of the sacroiliac joints, peripheral joints, and spine. The production of IL-22 goes through the transcription factors aryl hydrocarbon receptor (AhR) and RORgt as for Th17 (but with induced IL-22 mRNA expression less important for the latter) These results suggest that differentiation to either of these two cell types relies on RAR. A small subpopulation of IL-17A–producing iNKTs has been described in mice These IL-17+ iNKT cells express the RORgT transcription factor IL-23R and the chemokine receptor CCR6 [39,40,41,42]. This phenomenon induces a release of other pro-inflammatory factors (such as cytokines, chemokines, and matrix metalloproteinases) by mesenchymal and myeloid cells, allowing neutrophil recruitment and activation: the “neutrostat” system [68]. A recent work from our group confirmed that stimulated neutrophils from SpA patients were unable to express IL-17 A or IL-17F, both at the mRNA and protein levels (personal data)
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