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Elevated serum interleukin-27 levels in patients with systemic sclerosis: association with T cell, B cell and fibroblast activation
  1. Ayumi Yoshizaki1,
  2. Koichi Yanaba1,
  3. Yohei Iwata1,
  4. Kazuhiro Komura2,
  5. Asako Ogawa1,
  6. Eiji Muroi1,
  7. Fumihide Ogawa1,
  8. Motoi Takenaka1,
  9. Kazuhiro Shimizu1,
  10. Minoru Hasegawa2,
  11. Manabu Fujimoto2,
  12. Shinichi Sato1,3
  1. 1Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
  2. 2Department of Dermatology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan
  3. 3Department of Dermatology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan
  1. Correspondence to Dr Shinichi Sato, Department of Dermatology, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan; satos-der{at}h.u-tokyo.ac.jp

Abstract

Objective To determine serum levels of interleukin 27 (IL-27) in patients with systemic sclerosis (SSc) and relate the results to the clinical features of SSc.

Methods Serum levels of IL-27 in 91 patients with SSc and the production of IL-27 by isolated monocytes were examined by ELISA. The expression of IL-27 receptor in the skin fibroblasts, B cells and T cells was quantified by real-time PCR. The effect of IL-27 on immunoglobulin G (IgG) production of B cells, IL-17 production of CD4 T cells and proliferation and collagen synthesis of fibroblasts was also analysed.

Results Serum IL-27 levels were raised in patients with SSc compared with healthy controls and correlated positively with the extent of skin and pulmonary fibrosis and immunological abnormalities. IL-27 levels also correlated positively with serum levels of hyaluronan, recently identified as an endogenous ligand for Toll-like receptors. The retrospective longitudinal analysis showed a tendency for serum IL-27 levels to be attenuated during the follow-up period. IL-27 production by cultured monocytes was increased by hyaluronan stimulation. IL-27 receptor expression was upregulated in the affected skin fibroblasts, B cells and CD4 T cells of patients with SSc. Moreover, IL-27 stimulation increased IgG production of B cells, IL-17 production of CD4 T cells and proliferation and collagen synthesis of fibroblasts in patients with SSc compared with those in healthy controls.

Conclusion These results suggest that IL-27 and its signalling in B cells, T cells and fibroblasts contributes to disease development in patients with SSc.

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Footnotes

  • Funding This work was supported by a grant for Research on Intractable Diseases from the Ministry of Health, Labour and Welfare of Japan (to AY and SS).

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the Nagasaki University Hospital.

  • Provenance and peer review Not commissioned; externally peer reviewed.