Statistics from Altmetric.com
A series of discoveries has transformed concepts of spondyloarthritis and proinflammatory cytokine interleukin-23 (IL-23) has taken centre stage. The IL-23 frenzy kicked off with the identification of single nucleotide polymorphisms in the IL-23 receptor (IL-23R) gene that are associated with ankylosing spondylitis (AS)1 and also with related disorders such as psoriasis, psoriatic arthritis and Crohn's disease. The most striking and direct evidence comes from an in vivo IL-23 overexpression study in mice that phenocopies the human disease and its Janus-faced characteristics: joint inflammation and structural damage presenting as new bone formation.2 Patient studies reported increased serum levels of IL-23 in AS3–5 and the presence of IL-23-positive cells was shown in facet joints of patients with AS.6 Direct clinical evidence comes from a prospective, open-label clinical trial with ustekinumab, an antibody binding to the shared p40 subunit of IL-23 and IL-127 and successful clinical trials targeting IL-17, one of the downstream cytokines associated with IL-23 signalling.8 Key to the hypothesis and evidence proposed in the mouse model is the presence of an IL-23 receptor-positive T-cell population in the enthesis of mice. As enthesitis is one of the main characteristics of AS and was proposed as the primary lesion,9 it is hard to ignore the potential key role of such cells. However, until now, these IL-23 receptor-positive cells have not yet been demonstrated in human samples.
Ciccia et al10 report on the presence of a population of IL-23R-positive innate lymphoid cells (ILCs) in the gut, peripheral blood, synovial fluid and bone marrow of patients with AS. Numbers of such cells are increased as compared with different controls and their surface characteristics show similarities with the mouse cells identified earlier. However, these ILCs are a rare cell type whose significance in human disease is as …
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.