A Truncated IL‐17RC Peptide Ameliorates Synovitis and Bone Destruction of Arthritic Mice

Du, Yuxuan; Tong, Yulong; Mei, Wentong; Jia, Junhui; Niu, Menglin; Cao, Wei; Lou, Weiwei; Li, Shentao; Li, Zhanguo; Stinson, William A.; Yuan, Huatang; Zhao, Weiming

doi:10.1002/adhm.201600668

Cited by 12 publications

(5 citation statements)

References 43 publications

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“…Mouse and rat knee joints were removed postmortem, stored in 10% neutral formalin, decalcified in 20% ethylenediaminetetraacetic acid (EDTA) for 4 weeks, then dehydrated and embedded in paraffin. The sections were stained with hematoxylin & eosin (HE) and tartrate-resistant acid phosphatase (TRAP) before histopathological analysis 65 .…”

Section: Methodsmentioning

confidence: 99%

HIF1α inhibition facilitates Leflunomide-AHR-CRP signaling to attenuate bone erosion in CRP-aberrant rheumatoid arthritis

Liang

Lü

et al. 2019

Nat Commun

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Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by progressive bone erosion. Leflunomide is originally developed to suppress inflammation via its metabolite A77 1726 to attenuate bone erosion. However, distinctive responsiveness to Leflunomide is observed among RA individuals. Here we show that Leflunomide exerts immunosuppression but limited efficacy in RA individuals distinguished by higher serum C-reactive protein (CRPHigher, CRPH), whereas the others with satisfactory responsiveness to Leflunomide show lower CRP (CRPLower, CRPL). CRP inhibition decreases bone erosion in arthritic rats. Besides the immunomodulation via A77 1726, Leflunomide itself induces AHR-ARNT interaction to inhibit hepatic CRP production and attenuate bone erosion in CRPL arthritic rats. Nevertheless, high CRP in CRPH rats upregulates HIF1α, which competes with AHR for ARNT association and interferes Leflunomide-AHR-CRP signaling. Hepatocyte-specific HIF1α deletion or a HIF1α inhibitor Acriflavine re-activates Leflunomide-AHR-CRP signaling to inhibit bone erosion. This study presents a precision medicine-based therapeutic strategy for RA.

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Section: Methodsmentioning

confidence: 99%

HIF1α inhibition facilitates Leflunomide-AHR-CRP signaling to attenuate bone erosion in CRP-aberrant rheumatoid arthritis

Liang

Lü

et al. 2019

Nat Commun

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“…Soluble IL-17RC protein, which is a common receptor subunit for IL-17 and IL-17F, has been reported to exist and applied in rheumatoid arthritis via intraperitoneal injection. It can act as a decoy receptor for IL-17 and IL-17F, and inhibit downstream signal transduction, and ultimately prevent various inﬂammatory disorders [ 31 ]. Although the crucial roles of IL-17 and IL-17F in allergic airway inflammation have been extensively explored [ 32 ], reports on the potential role of their receptor IL-17RC subunit in allergic asthma is limited.…”

Section: Discussionmentioning

confidence: 99%

Self-assembled chitosan nanoparticles for intranasal delivery of recombinant protein interleukin-17 receptor C (IL-17RC): preparation and evaluation in asthma mice

Zhang

Wang

2021

Bioengineered

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Asthma is mentioned as a chronic airway inflammatory disease, whose pathogenesis is complicated. The promotion of inflammation in asthma by IL-17A and IL-17F has been confirmed. In addition to covalent homodimers, both cytokines are also able to form heterodimers, further inducing downstream pathways via binding to the IL-17RA and IL-17RC receptor complex. In recent years, IL-17RA and its signal transduction pathway have been extensively researched. IL-17RC, however, remains relatively unexplored. In the present study, we self-assembled chitosan (CS) nanoparticles for intranasal delivery of recombinant protein IL-17RC (rIL-17RC) and preliminarily investigated its effect on a murine model of allergic asthma induced by ovalbumin (OVA). rIL-17RC was produced by the prokaryotic expression system and encapsulated into the CS nanoparticles via ionic cross-linking technique. The results showed that CS-RC nanoparticles via intranasal intervention significantly caused inhibition of mucus secretion and airway inflammatory cell infiltration, and reduced IL-4, IL-17, IL-17F levels in BALF. Hence, delivering receptor proteins such as IL-17RC, through CS nanoparticles as a carrier, could be an attractive therapeutic intervention for asthma.

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“…In addition, the differentiation of osteoclast precursors into osteoclasts is suppressed by IL17RC [30]; IL17RC produced in response to compressive force may suppress osteoclastogenesis through the expression of OPG [31]. Additionally, IL17RC stimulates the secretion of other factors such as IL-6, tumor necrosis factor (TNF)-α and IL-1β in osteoclasts, further aggravating the inflammation [33].…”

Section: Discussionmentioning

confidence: 99%

IL17RC affects the predisposition to thoracic ossification of the posterior longitudinal ligament

Wang¹,

Liu²,

Liu³

et al. 2019

J Orthop Surg Res

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Background Thoracic ossification of the posterior longitudinal ligament (T-OPLL) can cause thoracic spinal stenosis, which results in intractable myelopathy and radiculopathy. The etiology of T-OPLL is unknown and the condition is difficult to treat surgically. Whole-genome sequencing identified a genetic variant at rs199772854 of the interleukin 17 receptor C (IL17RC) gene as a potentially pathogenic locus associated with T-OPLL. We aimed to determine whether the rs199772854A site mutation causes abnormal expression of the IL17RC in Han Chinese patients with T-OPLL and predict the possible pathogenic mechanisms of T-OPLL. Analyses were performed to determine whether IL17RC is involved in the pathogenicity of T-OPLL. Methods Peripheral blood and OPLL tissue were collected from a total of 72 patients with T-OPLL disease (36 patients carrying the rs199772854A site mutation in IL17RC and 36 wild-type patients). The expression of IL17RC was analyzed by enzyme-linked immunosorbent assay, reverse transcription-quantitative polymerase chain reaction, immunohistochemistry, and Western blotting. Results rs199772854A mutation resulted in markedly increased IL17RC gene expression levels in peripheral blood samples and the OPLL tissue obtained following clinical surgery ( P < 0.05). Conclusions The results suggest that the rs199772854A site mutation of IL17RC can significantly increase the expression of IL17RC. The IL17RC gene rs199772854A site polymorphism is a potential pathogenic mutation in T-OPLL disease, which may be associated with the occurrence of T-OPLL.

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A Truncated IL‐17RC Peptide Ameliorates Synovitis and Bone Destruction of Arthritic Mice

Cited by 12 publications

References 43 publications

HIF1α inhibition facilitates Leflunomide-AHR-CRP signaling to attenuate bone erosion in CRP-aberrant rheumatoid arthritis

HIF1α inhibition facilitates Leflunomide-AHR-CRP signaling to attenuate bone erosion in CRP-aberrant rheumatoid arthritis

Self-assembled chitosan nanoparticles for intranasal delivery of recombinant protein interleukin-17 receptor C (IL-17RC): preparation and evaluation in asthma mice

IL17RC affects the predisposition to thoracic ossification of the posterior longitudinal ligament

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