Elsevier

Joint Bone Spine

Volume 82, Issue 1, January 2015, Pages 1-4
Joint Bone Spine

Editorial
The IL-23/Th 17 pathway in spondyloarthritis: The Royal Road?

https://doi.org/10.1016/j.jbspin.2014.08.003Get rights and content

Section snippets

The IL-23/Th17 pathway

IL-23 is a dimeric cytokine whose two subunits are p40, which is shared with IL-12, and p19, which is specific to IL-23 [1]. The main sources of IL-23 are monocytes and dendritic cells stimulated by lipopolysaccharides and T-lymphocyte receptor activation. The main function of IL-23, together with IL-6 and TGF-β, consists of directing naive CD4+ T cells toward the Th17 phenotype. Th17 cells express surface receptors for TGF-β and IL-23. They produce several IL-17 isoforms (IL-17A through F),

IL-23 and Th17 in spondyloarthritis

Serum IL-17 levels were higher in patients with AS than in controls in two studies [3], [4] but not in another study [5]. Patients with AS may have similar serum IL-23 levels to those in controls but higher levels in joint fluid than in serum, suggesting local production [3].

Within facet-joint bone marrow specimens from patients with AS, the frequencies of IL-23 (p19)-positive cells [6] and IL-17 positive mononuclear cells [7] were elevated compared to patients with osteoarthritis. Furthermore,

Mechanisms of IL-23/Th17 involvement in spondyloarthritis

IL-23 may have multiple sources in patients with SpA. Pathogen-associated molecular patterns (PAMPs), such as bacterial lipopolysaccharides, flagellin, and peptidoglycan are recognized by cells via toll-like receptors (TLRs) as part of the innate immune response. Via PAMPs, microorganisms can activate monocytes and dendritic cells, thereby inducing IL-23 production [14]. Another mechanism of IL-23 overproduction may involve the behavior of HLA-B27. HLA-B27 folding is slow within the endoplasmic

Options for targeted treatment: proof of concept?

The IL-23/Th17 pathway can be targeted by therapeutic agents in a variety of manners, such as IL-23 blockade by monoclonal antibodies or soluble receptors and IL-23 receptor blockade by monoclonal antibodies. Potential targets include each of the IL-23 subunits (p40 and p19), IL-17A, and the IL-17A receptor. Several biological agents directed against these targets are available or are being developed and evaluated in patients with axial SpA or PsA (Table 2) [19], [20], [21], [22], [23], [24].

Discussion

The road may not be so easy to travel. Although the data discussed above establish a role for the IL-23/Th17 pathway in the development and progression of SpA, other mechanisms are probably involved also. Variations in results across studies, in particular, suggest complexity of the pathogenic factors. Thus, serum IL-17 and IL-23 levels elevation are correlated with disease activity (BASDAI) in one study [4] but serum IL-21 and IL-23 levels failed to correlate with clinical or magnetic

Disclosure of interest

The authors declare that they have no conflicts of interest concerning this article.

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