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AB0178 IL-12 Inhibits the Production of IL-10 in Patients with Sjogren Syndrome
  1. G. Yao,
  2. W. Chen,
  3. X. Tang,
  4. X. Feng,
  5. L. Sun
  1. Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China

Abstract

Background Interleukin (IL)-12, IL-23, IL-27, and IL-35 constitute a unique family of structurally-related, heterodimeric cytokines, which regulate immune response and inflammatory reactions. IL-12 family has been reported to be involved in the pathogenesis of autoimmune diseases [1-2]. However, the role of IL-12 family on Sjogren syndrome (SS) and related mechanisms remained to be elucidated.

Objectives Since the IL-12 family has been shown to regulate the generation of T regulatory 1 (Tr1) cells and Tr1 cells have been indicated a functional role in disease progress of SS through their secretion of the immunosuppressive cytokine IL-10[3-4]. The aim of the present study was to identify the specific members of IL-12 family involved in the pathogenesis of SS and to explore the relationship of IL-12 family cytokines with IL-10.

Methods 20 SS patients, 20 RA patients, 20 SLE patients and 20 healthy volunteers were recruited in the present study. Expressions of IL-12, IL-23, IL-27, and IL-35 in peripheral blood mononuclear cells (PBMCs) from patients with SS, RA, SLE and healthy controls were determined by quantitative PCR. Plasma levels of IL-12, IL-27 and IL-10 were detected by Enzyme-linked Immunosorbent Assay.

Results IL-12 and IL-27 mRNA significantly increased in PBMCs from patients with SS than healthy controls. Increased plasma levels of IL-12 and IL-27 have been confirmed in SS patients. Plasma IL-12 and IL-27 correlated with clinic indexes, such as anti-SSA, anti-SSB and ANA antibodies. IL-12 levels showed a negative correlation with plasma IL-10. However, no significant correlation was found between plasma IL-27 and IL-10 (Fig1).

Conclusions These findings suggested that IL-12 might have a pivotal role in the development and progression of SS through suppression of differentiation of IL-10-producing Tr1 cells. Therapeutic targeting IL-12 and Tr1 cells might be useful in the modulating of SS.

References

  1. Gee K, Guzzo C, Che Mat NF, et al. The IL-12 family of cytokined in infection, inflammation and autoimmune disorders. Inflamm Allergy Drug Targets, 2009, 8(1):40-52.

  2. Vignali DA, Kuchroo VK. IL-12 family cytokines: immunological playmakers. Nat Immunol, 2012, 13(8): 722-8

  3. Tsoumakidou M, Tousa S, Semitekolou M, et al. Tolerogenic signaling by pulmonary CD1c+ dendritic cells induces regulatory T cells in patients with chronic obstructive pulmonary disease by IL-27/IL-10/inducible costimulator ligand. J Allergy Clin Immunol, 2014, 134(4): 944-54.

  4. Pot C, Apetoh L, Kuchroo VK. Type 1 regulatory cells (Tr1) in autoimmunity. Semin Immunol, 2011, 23(3):202-8.

Disclosure of Interest None declared

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