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Interleukin 23 (IL-23) may play a key role in the pathogenesis of ankylosing spondylitis (AS). Patient studies reported increased serum levels of IL-23 in AS1–3 and the presence of IL-23 positive cells in facet joints of patients with AS.4 Moreover, in vivo overexpression of IL-23 in mice appears sufficient to phenocopy the human disease with inflammation and new bone formation and IL-23 receptor positive cells are found in entheses.5 The exact mechanism of how and where IL-23 production is induced and how it further contributes to the disease processes is not yet known. Different hypotheses have been proposed, such as HLA-B27 misfolding with activation of the unfolded protein response (UPR) as molecular drivers of IL-23 production. However, strong evidence of misfolding and UPR activation in patient samples is lacking.
Ciccia et al demonstrated that HLA-B27 misfolding specifically occurs in the gut of patients with AS and is accompanied by activation of autophagy rather than by activation of the UPR. Autophagy possibly causes the …