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OP0081 Aberrant Expression of IL-22RA1 on Hematopoietic Cells as Immunologically Signature of Primary Sjogren’s Syndrome and Sjogren-Associated Non-Hodgkin Lymphomas
  1. G. Guggino1,
  2. F. Ciccia1,
  3. A. Rizzo2,
  4. S. Raimondo3,
  5. A. Giardina1,
  6. F. Carubbi4,
  7. P. Cipriani4,
  8. G. Sireci3,
  9. R. Giacomelli4,
  10. R. Alessandro3,
  11. G. Triolo1
  1. 1Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia Sperimentale, University of Palermo
  2. 2Anatomia Patologica, Azienda Ospedaliera Ospedali riuniti Villa Sofia-Cervello
  3. 3Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, University of Palermo, Palermo
  4. 4Dipartimento di Scienze Cliniche Applicate e Biotecnologiche, University of L’Aquila, L’Aquila, Italy

Abstract

Background Interleukin (IL)-22 is a potent mediator of cellular inflammatory responses that has been recently reported to play a role in the pathogenesis of primary Sjogren’s Syndrome (p-SS) (1, 2) and of T and B lymphomas. IL-22 biological activity is initiated by binding to a cell-surface complex composed of two subunits, IL-22R1 and IL-10R2 receptor chains, and further regulated by interactions with a soluble binding protein, IL-22BP. Unlike the IL-10R2, which is constitutively expressed in many human tissues, IL-22R1 is not detectable in immune cells.

Objectives Aim of this study was to better characterize the role of IL-22 axis in the pathogenesis of p-SS and p-SS-associated lymphomas.

Methods Minor salivary gland biopsies were obtained from 30 patients with p-SS and 20 with non-specific chronic sialo-adenitis (n-SS) and evaluated by RT-PCR for IL-22, IL-22R1 and IL-22BP expression. The protein expression of IL-22, IL-22R1 and p-STAT3 was evaluated by immunohistochemistry and IL-22R1-expressing cells were caharcterized by confocal microscopy. Flow cytometry analysis of IL-22R1 expression was also conducted on peripheral blood mononuclear cells (PBMCs) from p-SS (n=30), n-SS (n=20), SLE (n=20) and rheumatoid arthritis (n=20) patients and normal controls (n=30). PBMCs isolated from 10 p-SS and 10 controls were also cultured with (or without) recombinant IL-22 and the modulation of the transcripts for pro-inflammatory cytokines was assessed by RT-PCR. Paraffin embedded sections of non-Hodgkin lymphomas from 5 p-SS patients were finally evaluated for the expression of IL-22R1.

Results IL-22, STAT3 and IL-22BP but not IL-22R1 transcript levels were significantly up-regulated in the inflamed salivary glands of p-SS but not in n-SS. Immunohistochemistry confirmed the increased salivary expression of IL-22 and p-STAT3 also demonstrating a significant increased protein levels of IL-22R1 in p-SS. Confocal microscopy analysis showed that IL-22R1 was aberrantly and strongly expressed in monocytes/macrophages infiltrating the p-SS salivary glands and these cells also co-expressed p-STAT3, suggesting the occurrence of autocrine activation of p-STAT3. CD68+ cells obtained from the peripheral blood also aberrantly expressed IL-22R1 in p-SS patients. IL-22R1 expression on cells of hematopoietic origin was never observed in control disease patients, n-SS and healthy controls. The stimulation with recombinant IL-22 of PBMCs from p-SS but not controls significantly up-regulated the expression of IL-17 and IL-22. Non-Hodgkin lymphoma tissues from p-SS patients were also characterized by the aberrant expression of IL-22R1 on macrophages and neoplastic B cells.

Conclusions The aberrant expression of IL-22RA1 on cells of hematopoietic origin seems to be a specific immunological signature of patients with p-SS and p-SS associated lymphomas and suggests a fundamental role of IL-22 signaling in the pathogenesis of p-SS and its neoplastic evolution. Targeting of IL-22 pathway may represent a successful therapeutic strategy in p-SS patients.

References

  1. Ciccia F, et al. Ann RheumDis 2012.

  2. Ciccia F, et al. Ann Rheum Dis 2012.

References

Disclosure of Interest None Declared

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