Decreased IL-27 expression in association with an increased Th17 response in Vogt-Koyanagi-Harada disease.
OBJECTIVE
IL-27 has emerged as an important regulator of proinflammatory T-cell responses in animal models. We investigated the pathophysiological role of IL-27 in Vogt-Koyanagi-Harada (VKH) disease.


METHODS
IL-27P28 and EBI3 mRNA expression in peripheral blood mononuclear cells (PBMCs) were assayed by RT-PCR. Cytokines in the serum and supernatants of PBMCs, naïve CD4(+) T cells and DC-T cocultures were assayed by ELISA. Flow cytometry was used to evaluate the frequencies of IL-17-producing CD4(+) T cells.


RESULTS
The active VKH patients showed a decreased IL-27P28 mRNA expression in PBMCs and lower IL-27 expression in the serum and supernatants of PBMCs, but higher Th17 cells in PBMCs. EBI3 mRNA expression was not different among the groups tested. Stimulation of naïve CD4(+) T cells under Th17 polarizing conditions showed a higher Th17 cell differentiation in active VKH patients. IL-27 significantly inhibited Th17 cell differentiation. IL-27-treated DCs showed a significant inhibition on Th17 differentiation. There was a significant defect in the Tr1 cell induction as measured by IL-10 in active VKH patients. Treatment with corticosteroids and cyclosporine A (CsA) resolved the intraocular inflammation in association with an upregulation of IL-27 and a downregulation of IL-17. In vitro experiments showed that corticosteroids, but not CsA, significantly upregulated the expression of IL-27.


CONCLUSIONS
The present study suggests that decreased IL-27 expression may result in a higher Th17 in active VKH patients, which may promote the autoimmune response observed in these patients. Manipulation of IL-27 may offer a novel target for treatment of this disease.
The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, Chongqing, P R China.
Chaokui
C
Wang
Yuan
Y
Tian
Bo
B
Lei
Xiang
X
Xiao
Zi
Z
Ye
Fuzhen
F
Li
Aize
A
Kijlstra
Peizeng
P
Yang
D000305:Adrenal Cortex Hormones / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism* / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D014606:Uveitis, Anterior / Q000188:drug therapy; D014607:Uveomeningoencephalitic Syndrome / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*
D000305:Adrenal Cortex Hormones; D016207:Cytokines; D007378:Interleukins; C464565:MYDGF protein, human; D012333:RNA, Messenger; D016753:Interleukin-10; D016572:Cyclosporine