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Evidence that autophagy, but not the unfolded protein response, regulates the expression of IL-23 in the gut of patients with ankylosing spondylitis and subclinical gut inflammation
  1. Francesco Ciccia1,
  2. Antonina Accardo-Palumbo2,
  3. Aroldo Rizzo2,
  4. Giuliana Guggino1,
  5. Stefania Raimondo3,
  6. AnnaRita Giardina1,
  7. Alessandra Cannizzaro2,
  8. Robert A Colbert4,
  9. Riccardo Alessandro3,
  10. Giovanni Triolo1
  1. 1Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia, Università di Palermo, Palermo, Italy
  2. 2Anatomia Patologica, Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy
  3. 3Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, Università di Palermo, Palermo, Italy
  4. 4National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland, USA
  1. Correspondence to Professor Giovanni Triolo, Department of Internal Medicine, Division of Rheumatology, University of Palermo, Piazza delle Cliniche 2, Palermo 90127, Italy; giovanni.triolo{at}unipa.it

Abstract

Objectives Interleukin (IL)-23 has been implicated in the pathogenesis of ankylosing spondylitis (AS). The aim of the study was to clarify the mechanisms underlying the increased IL-23 expression in the gut of AS patients.

Methods Consecutive gut biopsies from 30 HLA-B27+ AS patients, 15 Crohn's disease (CD) patients and 10 normal subjects were obtained. Evidence for HLA-B27 misfolding was studied. Unfolded protein response (UPR) and autophagy were assessed by RT-PCR and immunohistochemistry. The contribution of UPR and autophagy in the regulation of IL-23 expression was evaluated in in vitro experiments on isolated lamina propria mononuclear cells (LPMCs).

Results Intracellular colocalisation of SYVN1 and FHCs but not a significant overexpression of UPR genes was observed in the gut of AS patients. Conversely, upregulation of the genes involved in the autophagy pathway was observed in the gut of AS and CD patients. Immunohistochemistry showed an increased expression of LC3II, ATG5 and ATG12 but not of SQSTM1 in the ileum of AS and CD patients. LC3II was expressed among infiltrating mononuclear cells and epithelial cells resembling Paneth cells (PC) and colocalised with ATG5 in AS and CD. Autophagy but not UPR was required to modulate the expression of IL-23 in isolated LPMCs of AS patients with chronic gut inflammation, CD patients and controls.

Conclusions Our data suggest that HLA-B27 misfolding occurs in the gut of AS patients and is accompanied by activation of autophagy rather than a UPR. Autophagy appears to be associated with intestinal modulation of IL-23 in AS.

  • Spondyloarthritis
  • Inflammation
  • Cytokines

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