title: 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-γ) 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.
authors: Department of Medicine (463), Radboud University Nijmegen Medical Centre, Geert Grooteplein Zuid 8, 6525GA Nijmegen, The Netherlands.
authors: Marije
authors: M
authors: Oosting
authors: Hadewych
authors: H
authors: ter Hofstede
authors: Frank L
authors: FL
authors: van de Veerdonk
authors: Patrick
authors: P
authors: Sturm
authors: Bart-Jan
authors: BJ
authors: Kullberg
authors: Jos W M
authors: JW
authors: van der Meer
authors: Mihai G
authors: MG
authors: Netea
authors: Leo A B
authors: LA
authors: Joosten
mesh_terms: D025065:Borrelia burgdorferi / Q000378:metabolism; D002908:Chronic Disease; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000382:microbiology; D008193:Lyme Disease / Q000378:metabolism*; D011110:Polymorphism, Genetic; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C515500:IL23R protein, human; D020381:Interleukin-17; D018123:Receptors, Interleukin