Elevated serum interleukin-27 levels in patients with systemic sclerosis: association with T cell, B cell and fibroblast activation.
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.


CONCLUSIONS
These results suggest that IL-27 and its signalling in B cells, T cells and fibroblasts contributes to disease development in patients with SSc.
Yoshizaki
Ayumi
A
Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Yanaba
Koichi
K
Iwata
Yohei
Y
Komura
Kazuhiro
K
Ogawa
Asako
A
Muroi
Eiji
E
Ogawa
Fumihide
F
Takenaka
Motoi
M
Shimizu
Kazuhiro
K
Hasegawa
Minoru
M
Fujimoto
Manabu
M
Sato
Shinichi
S
D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D005260:Female; D005347:Fibroblasts / Q000276:immunology*; D005355:Fibrosis / Q000276:immunology; D005500:Follow-Up Studies; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis / Q000097:blood* / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D018123:Receptors, Interleukin / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000276:immunology*; D012867:Skin / Q000276:immunology / Q000473:pathology; D055815:Young Adult
C112441:IL27RA protein, human; D020381:Interleukin-17; D018123:Receptors, Interleukin; D003094:Collagen