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Role of interleukin-23 (IL-23) receptor signaling for IL-17 responses in human Lyme disease.

ABSTRACT: Interleukin-23 (IL-23) is known to play a crucial role in the development and maintenance of T helper 17 cells. It has been previously demonstrated that IL-17 is involved in experimental Lyme arthritis, caused by Borrelia burgdorferi bacteria. However, the precise role of the IL-23 receptor (IL-23R) for the B. burgdorferi-induced IL-17 responses or human Lyme disease has not yet been elucidated. IL-23R single nucleotide polymorphism (SNP) rs11209026 was genotyped using the TaqMan assay. Functional studies were performed using peripheral blood mononuclear cells, and cytokines were measured using enzyme-linked immunosorbent assay (ELISA). Dose-dependent production of IL-23 and IL-17 by B. burgdorferi could be observed. Interestingly, when IL-23 bioactivity was inhibited by a specific antibody against IL-23p19, IL-17 production was significantly downregulated. In contrast, production of gamma interferon (IFN-?) was not affected after the blockade of IL-23 activity. Moreover, individuals bearing a single nucleotide polymorphism in the IL-23R gene (Arg381Gln) produced significantly less IL-17 after B. burgdorferi stimulation compared with that of the individuals bearing the wild type. Despite lower IL-17 production, the IL-23R gene polymorphism did not influence the development of chronic Lyme disease in a cohort of patients with Lyme disease. This study demonstrates that IL-23R signaling is needed for B. burgdorferi-induced IL-17 production in vitro and that an IL-23R gene SNP leads to impaired IL-17 production. However, the IL-23R gene polymorphism is not crucial for the pathogenesis of chronic Lyme.

SUBMITTER: Oosting M

PROVIDER: S-EPMC3257938 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Role of interleukin-23 (IL-23) receptor signaling for IL-17 responses in human Lyme disease.

Oosting Marije M ter Hofstede Hadewych H van de Veerdonk Frank L FL Sturm Patrick P Kullberg Bart-Jan BJ van der Meer Jos W M JW Netea Mihai G MG Joosten Leo A B LA

Infection and immunity 20110906 11

Interleukin-23 (IL-23) is known to play a crucial role in the development and maintenance of T helper 17 cells. It has been previously demonstrated that IL-17 is involved in experimental Lyme arthritis, caused by Borrelia burgdorferi bacteria. However, the precise role of the IL-23 receptor (IL-23R) for the B. burgdorferi-induced IL-17 responses or human Lyme disease has not yet been elucidated. IL-23R single nucleotide polymorphism (SNP) rs11209026 was genotyped using the TaqMan assay. Function ...[more]

PMID: 21896776

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Project description:Background: Interleukin (IL)-17/IL-23 axis performs a prominent role in the pathogenesis of several autoimmune disorders. This study aimed to investigate the concentrations of IL-17 in patients with multiple sclerosis (MS) and its relationship with gender, medication, disease forms and single nucleotide polymorphisms (SNP) in IL-23R gene, including rs11209026 and rs1004819. Methods: The blood specimens were obtained from 135 healthy individuals and 135 MS patients. The patients exhibited relapsing-remitting (RRMS; n = 65), primary progressive (PPMS; n = 19), secondary progressive (SPMS; n = 35) or progressive relapsing (PRMS; n = 14) MS. The DNA was analyzed for SNPs using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and IL-17 concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Results: We have observed elevated serum IL-17 concentrations in MS patients compared with healthy individuals (P < 0.001). The men with MS had higher IL-17 concentrations than women patients (P < 0.050). Untreated patients had significantly higher IL-17 concentrations than healthy individuals and treated patients (P < 0.001 and P < 0.010, respectively). The IL-17 concentrations were significantly decreased in patients treated with interferon-? (IFN-?), methylprednisolone or both drugs as compared with untreated MS patients (P < 0.050, P < 0.020 and P < 0.050, respectively). The IL-17 concentrations were also significantly higher in patients with RRMS and PRMS compared with healthy individuals (P < 0.005 and P < 0.010, respectively). The genetic variations at SNPs rs11209026 and rs1004819 were not significantly different between healthy individuals and patients. The IL-17 concentrations were not influenced by genetic variations at investigated SNPs. Conclusion: These results indicated higher levels of IL-17 in MS patients that may be influenced by disease patterns, medication and gender. No association was observed between investigated SNPs and MS.

Dataset Information

Role of interleukin-23 (IL-23) receptor signaling for IL-17 responses in human Lyme disease.

Publications

Role of interleukin-23 (IL-23) receptor signaling for IL-17 responses in human Lyme disease.

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