IL-23 promotes CD4+ T cells to produce IL-17 in Vogt-Koyanagi-Harada disease.

Abstract

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.

CONCLUSION:

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.

CLINICAL IMPLICATIONS:

This study provides a new insight into the mechanism involved in the development of VKH disease.

• Authors: Wei Chi, Peizeng Yang, Bing Li, Changyou Wu, Haoli Jin, Xuefei Zhu, Lina Chen, Hongyan Zhou, Xiangkun Huang, Aize Kijlstra
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 119 Issue 5 Pg. 1218-24 (May 2007) ISSN: 0091-6749 [Print] United States
• PMID: 17335887 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-17
• Interleukin-23
• RNA, Messenger
• Interleukin-4
• Interferon-gamma

Topics

• Adult
• CD4-Positive T-Lymphocytes (immunology, metabolism)
• Enzyme-Linked Immunosorbent Assay
• Female
• Humans
• Interferon-gamma (immunology, metabolism)
• Interleukin-17 (immunology, metabolism)
• Interleukin-23 (immunology, metabolism)
• Interleukin-4 (immunology, metabolism)
• Leukocytes, Mononuclear (immunology, metabolism)
• Male
• RNA, Messenger (analysis)
• Reverse Transcriptase Polymerase Chain Reaction
• Uveomeningoencephalitic Syndrome (immunology, metabolism)