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

doi:10.1016/j.jaci.2007.01.010

Journal of Allergy and Clinical Immunology

Volume 119, Issue 5, May 2007, Pages 1218-1224

https://doi.org/10.1016/j.jaci.2007.01.010 Get rights and content

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-γ 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-γ 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-γ 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.

Section snippets

Patients

Twenty-five patients with VKH disease (13 men and 12 women) with an average age of 39 years and 16 healthy individuals (9 men and 7 women) with an average age of 40 years were included in the study. The diagnosis of VKH disease was made according to the diagnostic criteria revised for VKH disease in an international committee on nomenclature.¹⁹ Fifteen patients showed active recurrent intraocular inflammation (active uveitis stage). These patients had received only prednisone at a low dose

Expression of IL-23p19 mRNA in PBMCs of patients with VKH disease and normal control subjects

The PCR products showed a 99.6% homology with the known IL-23p19 sequence. The expression of the IL-23p19 mRNA was normalized by respective β-actin mRNA. The average intensity ratio of IL-23p19 PCR product/β-actin product (0.285 ± 0.032) in patients with VKH disease with active uveitis (n = 9) was significantly higher than that in patients with VKH disease with inactive uveitis (0.137 ± 0.027; n = 9; P = .025) and in normal control subjects (0.174 ± 0.047; n = 7; P = .015; Fig 1, A). Moreover,

Discussion

In the present study, we found an increased expression of IL-23p19 mRNA in PBMCs and an elevated level of IL-23 protein in the serum and supernatants of cultured PBMCs of patients with VKH disease with active uveitis. There was a markedly enhanced production of IL-17 by PBMCs and CD4⁺ T cells of patients with VKH disease with active uveitis after polyclonal stimulation. We also found that IL-23 promoted IL-17 production by PBMCs and CD4⁺ T cells of patients with VKH disease and normal control

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Citation Excerpt :
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Supported by the Fund for National Natural Science Foundation (30572004), the Natural Science Foundation for Research Groups of Guangdong Province (2005-04), the Fund for Innovative Research Groups (30321004), and the Key Project of National Natural Science Foundation (30630064).

Disclosure of potential conflict of interest: All of the authors received support from the Fund for National Natural Science Foundation, the Natural Science Foundation for Research Groups of Guangdong Province, the Innovative Research Groups, and the Key Project of National Natural Science Foundation.

View full text

Basic and clinical immunologyIL-23 promotes CD4+ T cells to produce IL-17 in Vogt-Koyanagi-Harada disease

Background

Objective

Methods

Results

Conclusion

Clinical implications

Section snippets

Patients

Expression of IL-23p19 mRNA in PBMCs of patients with VKH disease and normal control subjects

Discussion

Immunity

J Invest Dermatol

J Invest Dermatol

Surv Ophthalmol

Am J Ophthalmol

Cell Biol Int

J Biol Chem

J Allergy Clin Immunol

Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain

Nature

Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation

J Exp Med

IL-23 drives a pathogenic T cell population that induces autoimmune inflammation

J Exp Med

T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines

J Exp Med

Interleukin-17 in rheumatoid arthritis: if T cells were to contribute to inflammation and destruction through synergy

Arthritis Rheum

Increased expression of interleukin-23 p19 and p40 in lesional skin of patients with psoriasis vulgaris

J Exp Med

Interleukin-17 family members and inflammation

Immunity

Human interleukin-17: a T cell–derived proinflammatory cytokine produced by the rheumatoid synovium

Arthritis Rheum

Basic and clinical immunology
IL-23 promotes CD4⁺ T cells to produce IL-17 in Vogt-Koyanagi-Harada disease