دورية أكاديمية
Aberrant intestinal microbiota due to IL-1 receptor antagonist deficiency promotes IL-17- and TLR4-dependent arthritis
| العنوان: | Aberrant intestinal microbiota due to IL-1 receptor antagonist deficiency promotes IL-17- and TLR4-dependent arthritis |
|---|---|
| المؤلفون: | Rogier, Rebecca, Ederveen, Thomas H.A., Boekhorst, Jos, Wopereis, Harm, Scher, Jose U., Manasson, Julia, Frambach, Sanne J.C.M., Knol, Jan, Garssen, Johan, van der Kraan, Peter M., Koenders, Marije I., van den Berg, Wim B., van Hijum, Sacha A.F.T., Abdollahi-Roodsaz, Shahla |
| المصدر: | Microbiome 5 (2017) 1 ; ISSN: 2049-2618 |
| سنة النشر: | 2017 |
| المجموعة: | Wageningen UR (University & Research Centre): Digital Library |
| مصطلحات موضوعية: | Autoimmune arthritis, IL-1 receptor antagonist, Microbiota, T helper 17 cells, Toll-like receptors |
| الوصف: | BACKGROUND: Perturbation of commensal intestinal microbiota has been associated with several autoimmune diseases. Mice deficient in interleukin-1 receptor antagonist (Il1rn -/- mice) spontaneously develop autoimmune arthritis and are susceptible to other autoimmune diseases such as psoriasis, diabetes, and encephalomyelitis; however, the mechanisms of increased susceptibility to these autoimmune phenotypes are poorly understood. We investigated the role of interleukin-1 receptor antagonist (IL-1Ra) in regulation of commensal intestinal microbiota, and assessed the involvement of microbiota subsets and innate and adaptive mucosal immune responses that underlie the development of spontaneous arthritis in Il1rn -/- mice.RESULTS: Using high-throughput 16S rRNA gene sequencing, we show that IL-1Ra critically maintains the diversity and regulates the composition of intestinal microbiota in mice. IL-1Ra deficiency reduced the intestinal microbial diversity and richness, and caused specific taxonomic alterations characterized by overrepresented Helicobacter and underrepresented Ruminococcus and Prevotella. Notably, the aberrant intestinal microbiota in IL1rn -/- mice specifically potentiated IL-17 production by intestinal lamina propria (LP) lymphocytes and skewed the LP T cell balance in favor of T helper 17 (Th17) cells, an effect transferable to WT mice by fecal microbiota. Importantly, LP Th17 cell expansion and the development of spontaneous autoimmune arthritis in IL1rn -/- mice were attenuated under germ-free condition. Selective antibiotic treatment revealed that tobramycin-induced alterations of commensal intestinal microbiota, i.e., reduced Helicobacter, Flexispira, Clostridium, and Dehalobacterium, suppressed arthritis in IL1rn -/- mice. The arthritis phenotype in IL1rn -/- mice was previously shown to depend on Toll-like receptor 4 (TLR4). Using the ablation of both IL-1Ra and TLR4, we here show that the aberrations in the IL1rn -/- microbiota are partly TLR4-dependent. We further identify a role for TLR4 ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://edepot.wur.nl/440237Test; https://research.wur.nl/en/publications/aberrant-intestinal-microbiota-due-to-il-1-receptor-antagonist-deTest |
| DOI: | 10.1186/s40168-017-0278-2 |
| الإتاحة: | https://doi.org/10.1186/s40168-017-0278-2Test https://research.wur.nl/en/publications/aberrant-intestinal-microbiota-due-to-il-1-receptor-antagonist-deTest |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test/ ; Wageningen University & Research |
| رقم الانضمام: | edsbas.A2C09C87 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s40168-017-0278-2 |
|---|