IL-23 promotes CD4+ T cells to produce IL-17 in Vogt-Koyanagi-Harada disease.
BACKGROUND
Vogt-Koyanagi-Harada (VKH) disease is a systemic refractory autoimmune disease. IL-23 has been thought to play a critical role in autoimmune disease through inducing the development of IL-17-producing CD4(+) T cells.


OBJECTIVE
To investigate the expression of IL-23 and IL-17 and the influence of IL-23 on IL-17 production in patients with VKH disease.


METHODS
Blood samples were taken from 25 patients with VKH disease and 16 healthy controls. Peripheral blood mononuclear cells (PBMCs) were subjected to analysis of IL-23p19 mRNA and IL-23 protein expression using RT-PCR and ELISA, respectively. The IL-17 levels in the supernatants of PBMCs and CD4(+) T cells cultured in the absence or presence of recombinant (r)IL-23, rIL-12, or anti-IFN-gamma were determined by ELISA.


RESULTS
The patients with VKH disease with active uveitis showed an elevated level of IL-23p19 mRNA in PBMCs, higher IL-23 in the serum and supernatants of PBMCs, and increased production of IL-17 by polyclonally stimulated PBMCs and CD4(+) T cells. Recombinant IL-23 significantly enhanced IL-17 production, whereas rIL-12 and IFN-gamma inhibited IL-17 production. More importantly, IL-17 production was significantly increased in patients with active uveitis in the presence of rIL-23. Both rIL-23 and rIL-12 enhanced IFN-gamma production.


CONCLUSIONS
The results suggest that IL-23-stimulated production of IL-17 by CD4(+) T cells may be responsible for the development of uveitis seen in patients with VKH disease.


CONCLUSIONS
This study provides a new insight into the mechanism involved in the development of VKH disease.
Chi
Wei
W
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Uveitis Study Center, Sun Yat-sen University, Guanzhou, China.
Yang
Peizeng
P
Li
Bing
B
Wu
Changyou
C
Jin
Haoli
H
Zhu
Xuefei
X
Chen
Lina
L
Zhou
Hongyan
H
Huang
Xiangkun
X
Kijlstra
Aize
A
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D053759:Interleukin-23 / Q000276:immunology / Q000378:metabolism*; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014607:Uveomeningoencephalitic Syndrome / Q000276:immunology / Q000378:metabolism*
D020381:Interleukin-17; D053759:Interleukin-23; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma