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OP0166 Il-27 Participates in Sjogren's Syndrome by Regulating Lymphocyte Subsets
  1. J. Qi,
  2. B. Shi,
  3. Z. Zhang,
  4. R. Feng,
  5. W. Chen,
  6. G. Yao,
  7. Y. Hou,
  8. L. Sun
  1. Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China

Abstract

Background Primary Sjogren's syndrome (pSS) is a chronic, systemic autoimmune disorder characterized by inflammation of exocrine glands and functional impairment of the salivary and lacrimal glands [1]. The pathogenesis of pSS is complicated with many respects remaining elusive. Interleukin-27 (IL-27) is a new member of the IL-12 cytokine family. It is largely secreted by activated antigen-presenting cells, such as macrophages and dendritic cells (DCs). IL-27 participates in multiple autoimmune diseases by regulating T lymphocyte subsets. Recent studies showed that IL-27 was involved in anti-inflammatory functions in SS [2]. However, the underlying mechanism of IL-27 in SS is still unknown.

Objectives In the present study, the changes of lymphocyte subsets were studied in Il-27 knock-out and wild-type pSS models and pSS patients for the purpose to explore the specific mechanism of IL-27 in pSS and provide the basis for clinical treatment.

Methods The NOD mice, Il-27 knockout (Il-27–/–) mice, Il-27 knockout mice with recombinant IL-27 treatment were studied. The saliva flow rates, weight, weight of submandibular glands and spleens were detected. Murine submandibular glands were fixed and paraffin sections were used for hematoxylin and eosin staining. The lymphocyte subsets of spleens from experimental mice and the peripheral blood from pSS patients were measured by flow-cytometric assay.

Results Compared to WT NOD mice, the saliva flow rates decreased significantly, and the indexes of submandibular glands and spleens increased significantly in Il-27–/– mice (Fig 1A-E). The histological results showed that the number of lymphocytic infiltrates in submandibular glands of WT NOD was lower than Il-27–/– mice (Fig 1F). The splenic-Treg cells decreased significantly, but the levels of splenic Th17 and B cells increased significantly in Il-27–/– mice. After IL-27 treatment, the saliva flow rates, submandibular glands, Treg and Th17 cells were partially reversed in Il-27–/– mice (Fig 1G-M). Consistent with above observations, the changes of Terg and Th17 cells in pSS patients showed similar pattern. The Th2, Tfh and plasma cells increased significantly, whilst the B cells decreased significantly in pSS patients (Fig 1N-T). Compared with healthy control, the serum IL-27 decreased in pSS patients.

Conclusions In general, these findings indicated that IL-27 deficiency deteriorated the disease symptoms of pSS and resulted in changes of Th17/Treg balance. In addition, pSS patients showed similar lymphocyte imbalance. Our data suggested that IL-27 might play an important role on the development and pathogenesis of pSS through regulating lymphocyte subsets, and targeting IL-27 and Th17/Treg balance may be a new direction of pSS treatment.

  1. Xu J, Wang D, Liu D, et al. Allogeneic mesenchymal stem cell treatment alleviates experimental and clinical Sjogren syndrome. Blood, 2012, 120(15): 3142–3151.

  2. Lee BH, Carcamo WC, Chiorini JA, et al. Gene therapy using IL-27 ameliorates Sjögren's syndrome-like autoimmune exocrinopathy. Arthritis Res Ther, 2012, 14(4): R172.

Disclosure of Interest None declared

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