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Biological and genetic evaluation of IL-23/IL-17 pathway in ankylosing spondylitis patients.

ABSTRACT: Ankylosing spondylitis is the most common form of the chronic inflammatory disease group known as spondyloarthritides. Recent discoveries of the CD4+ Th17 cells and IL-23/IL-17 axis have changed the paradigms in many autoimmune diseases. In this study, we aimed to evaluate the importance of IL-23/IL-17 pathway and IL-23 receptor polymorphism in the pathogenesis of ankylosing spondylitis. Blood samples for this study were obtained from 109 ankylosing spondylitis patients and 40 healthy control subjects. Serum levels of TNF-?, IL-6, IL-17, and IL-23 were measured by the ELISA method. The IL-23R gene polymorphisms rs11209026 (Arg381Gln) and rs4131362 (Val362Ile) were performed by the Sanger Sequence method. IL-6 levels were higher in the active and inactive ankylosing spondylitis groups than in the control group. However, levels of IL-17 and IL-23 were lower in the patient group. The frequency of IL-23R gene rs11209026 and rs4131362 polymorphism were 3.7% and 8.3% in the patient, respectively. As a result, dysregulation of the IL-23 / IL-17 pathway, which is caused by reduced levels of IL-17 and IL-23 in systemic circulation in patients with ankylosing spondylitis, may contribute to the pathogenesis of the disease by systemically producing chronic autoimmune inflammation.

SUBMITTER: Deveci H

PROVIDER: S-EPMC7050057 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Biological and genetic evaluation of IL-23/IL-17 pathway in ankylosing spondylitis patients.

Deveci Hulya H Turk Ayla Cagliyan AC Ozmen Zeliha Cansel ZC Demir Ayse Kevser AK Say Coskun Safiye Umut SU

Central-European journal of immunology 20190101 4

Ankylosing spondylitis is the most common form of the chronic inflammatory disease group known as spondyloarthritides. Recent discoveries of the CD4+ Th17 cells and IL-23/IL-17 axis have changed the paradigms in many autoimmune diseases. In this study, we aimed to evaluate the importance of IL-23/IL-17 pathway and IL-23 receptor polymorphism in the pathogenesis of ankylosing spondylitis. Blood samples for this study were obtained from 109 ankylosing spondylitis patients and 40 healthy control su ...[more]

PMID: 32140056

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Project description:It is very important to understand the communication and interaction mechanisms between the host and its resident microorganisms on host physiology and for precise diagnosis and treatment. Although intestinal fungi and bacteria dysbiosis is increasingly linked to ankylosing spondylitis (AS), their mechanisms of action have been rarely illustrated. In this paper, fecal samples from 10 AS monkeys and 10 healthy controls were collected to systematically characterize the gut mycobiota and microbiota in AS monkeys by 16S rRNA and ITS2 DNA sequencing. Our results showed the gut fungi of Kazachstania pintolopesii, Saccharomycetaceae, Kazachstania, and Saccharomyceteles. Saccharomycetes were specially enriched in AS, and the microbiota of AS monkeys was characterized by an increased abundance of Clostridia, Clostridiales, Ruminococcaceae, and Prevotella 2, using Line Discriminant Analysis Effect Size. Compared to healthy controls, decreased ITS2/16S biodiversity ratios and altered bacterial-fungal interkingdom networks were observed in AS monkeys. Oral administration of K. pintolopesii activates IL-17RA pathway and induce inflammatory reaction in the colonic tissue of C57BL/6 mice, as well as multiple AS phenotypes, including fungal and bacterial dysbiosis, immune responses of NK cells, platelets, T cells, leukocytes, B-cell activation, rheumatoid arthritis, and inflammatory bowel disease. We also found the secreted products of K. pintolopesii could activate the IL-17RA pathway, which induces PANoptosis in macrophage RAW264.7 cells. Much worse, the PANoptosis products could promote the proliferation and morphological changes of K. pintolopesii, which resulted in much more K. pintolopesii and a severe inflammatory reaction. Interestingly, the inflammatory factor TNF-α can promote the morphological transformation of Candida albicans and K. pintolopesii, which is worthy of further study. The characteristic fungi in all these findings implied that fungal and bacterial dysbiosis have a close link to AS and that their communication and interaction indeed play an important role in autoimmune responses, and K. pintolopesii could be a potential marker microorganism in AS, although its specific mechanism is not fully elucidated.

Dataset Information

Biological and genetic evaluation of IL-23/IL-17 pathway in ankylosing spondylitis patients.

Publications

Biological and genetic evaluation of IL-23/IL-17 pathway in ankylosing spondylitis patients.

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