Article ; Online: Innate Cells: The Alternative Source of IL-17 in Axial and Peripheral Spondyloarthritis?
2021 Volume 11, Page(s) 553742
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 ... ...
| 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. |
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| MeSH term(s) | Antibodies, Monoclonal, Humanized/therapeutic use ; Arthritis, Psoriatic/drug therapy ; Arthritis, Psoriatic/immunology ; Arthritis, Psoriatic/pathology ; Humans ; Immunity, Innate/drug effects ; Interleukin-17/immunology ; Interleukin-23/immunology ; Spondylarthritis/drug therapy ; Spondylarthritis/immunology ; Spondylarthritis/pathology |
| Chemical Substances | Antibodies, Monoclonal, Humanized ; Interleukin-17 ; Interleukin-23 ; ixekizumab (BTY153760O) ; secukinumab (DLG4EML025) |
| Language | English |
| Publishing date | 2021-01-08 |
| Publishing country | Switzerland |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't ; Review |
| ZDB-ID | 2606827-8 |
| ISSN | 1664-3224 ; 1664-3224 |
| ISSN (online) | 1664-3224 |
| ISSN | 1664-3224 |
| DOI | 10.3389/fimmu.2020.553742 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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