The IL-23–IL-17 immune axis: from mechanisms to therapeutic testing

Gaffen, Sarah L.; Jain, Renu; Garg, Abhishek V.; Daniel, J.

doi:10.1038/nri3707

Cited by 1,258 publications

(1,226 citation statements)

References 181 publications

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“…In addition, smokers have greater numbers of CD4+ IL-17+ T cells in the lung tissue than non-smokers [24]. If a similar phenomenon also occurred in the periodontium it could conceivably influence local and circulating levels of IL-17A and IL-17E.…”

Section: Discussionmentioning

confidence: 98%

The effect of periodontal scaling and root polishing on serum IL-17E concentrations and the IL-17A:IL-17E ratio

et al. 2016

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. (2016) The effect of periodontal scaling and root polishing on serum IL-17E concentrations and the IL-17A: IL-17E ratio. Clinical Oral Investigations, 20(9), pp. 2529-2537. (doi:10.1007/s00784-016-1749 This is the author's final accepted version.There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.http://eprints.gla.ac.uk/116253/ The serum IL-17A:IL-17E ratio has previously been demonstrated to be a clinical marker of periodontitis. The aim of this study was to determine the effects of non-surgical periodontal treatment on the serum IL-17A:IL-17E ratio. MATERIALS AND METHODS:Forty chronic periodontitis patients completed this study and received periodontal treatment comprising scaling and root planing plus ultrasonic debridement. Clinical data were recorded at baseline, six weeks (R1) after treatment completion (full-mouth or quadrant-scaling and root planing) and 25 weeks after baseline (R2). Serum samples were taken at each time point and cytokines concentrations determined by ELISA. RESULTS:Following treatment, statistically significant reductions were noted in clinical parameters. However, IL-17A and IL-17E concentrations were significantly greater than baseline values before-and after-adjusting for smoking. The IL-17A:IL-17E ratio was lower at R1 and R2. Serum IL-6 and TNF levels were significantly lower at R1 only. Also exclusively at R1, serum IL-17A and IL-17E correlated positively with clinical parameters, while the IL-17A:IL-

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Section: Discussionmentioning

confidence: 98%

The effect of periodontal scaling and root polishing on serum IL-17E concentrations and the IL-17A:IL-17E ratio

et al. 2016

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“…However, when CyA was abruptly switched to infliximab, PASI scores decreased without worsening of psoriasis,4 suggesting that biologics with a rapid response do not require co‐administration of CyA for a smooth transition. Accumulating evidence has shown that new anti‐IL‐17A therapies offer a more reliable response with an improved efficacy 10. Furthermore, a recent study investigating the mechanism of relapse induced by CyA withdrawal showed that production of IL‐17A was increased after discontinuation of CyA in the experimental autoimmune encephalomyelitis mice and the severity of relapse was reduced by treatment with anti‐IL‐17A antibody, suggesting that a burst of IL‐17A production is at least partially responsible for the relapse 25.…”

Section: Discussionmentioning

confidence: 99%

Secukinumab improves psoriasis symptoms in patients with inadequate response to cyclosporine A: A prospective study to evaluate direct switch

Ohtsuki

Morita

Igarashi

et al. 2017

The Journal of Dermatology

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There are limited data on the safety and efficacy of switching to secukinumab from cyclosporine A (CyA) in patients with psoriasis. The purpose of the present study was to assess the efficacy and safety of secukinumab for 16 weeks after direct switching from CyA in patients with moderate‐to‐severe psoriasis. In this multicenter, open‐label, phase IV study, 34 patients with moderate‐to‐severe psoriasis and inadequate response to CyA received secukinumab 300 mg s.c. at baseline and weeks 1, 2, 3, 4, 8 and 12. The primary end‐point was ≥75% improvement from baseline in Psoriasis Area and Severity Index score (PASI 75) at week 16. The efficacy of secukinumab treatment was evaluated up to week 16, and adverse events (AE) were monitored during the study. The primary end‐point of the PASI 75 response at week 16 was achieved by 82.4% (n = 28) of patients receiving secukinumab. Early improvements were observed with secukinumab, with PASI 50 response of 41.2% at week 2 and PASI 75 response of 44.1% at week 4. AE were observed in 70.6% (n = 24) of patients, and there were no serious AE or deaths reported in the entire study period. Secukinumab showed a favorable safety profile consistent with previous data with no new or unexpected safety signals. The results of the present study show that secukinumab is effective in patients with psoriasis enabling a smooth and safe direct switch from CyA to biological therapy.

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“…In this feedback mechanism, macrophages and dendritic cells phagocytose apoptotic neutrophils [47][48][49] , curbing the secretion of IL-23 46 -a cytokine that controls IL-17 expression by αβ T cells, γδ T cells, innate lymphoid cells and other lymphocytes 50,51 . Because IL-17 is upstream of G-CSF 52,53 , lower levels of IL-17 equate to reduced expression of G-CSF and steady-state release of neutrophils from the bone marrow 46 .…”

Section: Neutrophil Retention and Release From Bone Marrowmentioning

confidence: 99%

Neutrophils in cancer: neutral no more

2016

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SummaryNeutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view.The traditionally held belief that neutrophils are inert bystanders is being challenged by recent literature. Emerging evidence indicates that tumors manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumor behavior. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets. 2The name neutrophil -given to polymorphonuclear, granulocytic cells by Paul Ehrlich in the late 19th century -is based on the inability of these cells to retain acidic or basic dyes and for their preferential uptake of pH neutral dyes 1 . Although their neutral staining led to the identification of these cells, neutrophils in the cancer setting are anything but neutral.Neutrophils in tumor-bearing hosts can oppose or potentiate cancer progression. These two types of behavior are controlled by signals emanating from cancer cells or stromal cells within the tumor microenvironment, which educate neutrophils to execute the demise of the tumor or facilitate support networks that lead to its expansive spread. These functions can occur locally in or around the tumor microenvironment, as well as systemically in distant organs.Until the past few years, other immune cells such as macrophages have overshadowed the role of neutrophils in cancer. But recent studies and the development of new genetic tools have provided the cancer community with new insights into the profound influence of these dynamic cells by uncovering distinct capabilities for neutrophils throughout each step of carcinogenesis: from tumor initiation to primary tumor growth to metastasis.During these processes, neutrophils take on different phenotypes and sometimes opposing functions. Emerging evidence also indicates that these cells are highly influential, and are able to change the behavior of other tumor-associated cell types -primarily other immune cells. In this Review, we focus on how tumors manipulate the generation and release of neutrophils from the bone marrow. We discuss the mechanisms identified in animal models by which neutrophils participate in tumor initiation, growth and metastasis. Finally, we highlight the potential of these cells as clinical biomarkers and therapeutic targets. In humans, neutrophils are the most abundant immune cell population, representing 50-70% of all leukocytes. Over 10 11 neutrophils may be produced per day 2 , and tumors can increase this number by even more. Indeed, patients with various cancer types, including but not limited to breast, lung and colorectal cancer, often exhibit increased numbers of circulating neutrophils 3,4 . Recent studies have identified key pathways that tumors exploit to disrupt normal neutrophil homeostasis and these are discuss...

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The IL-23–IL-17 immune axis: from mechanisms to therapeutic testing

Cited by 1,258 publications

References 181 publications

The effect of periodontal scaling and root polishing on serum IL-17E concentrations and the IL-17A:IL-17E ratio

The effect of periodontal scaling and root polishing on serum IL-17E concentrations and the IL-17A:IL-17E ratio

Secukinumab improves psoriasis symptoms in patients with inadequate response to cyclosporine A: A prospective study to evaluate direct switch

Neutrophils in cancer: neutral no more

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