Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis

Pandey R, Al-Nuaimi Y, Mishra RK, Spurgeon SK, Goodfellow M. 2021. Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis. Scientific Reports. 11, 2204.

Download
OA 2021_ScientificReports_Pandey.pdf 2.89 MB

Journal Article | Published | English

Scopus indexed
Author
Pandey, Rakesh; Al-Nuaimi, Yusur; Mishra, Rajiv KumarIST Austria; Spurgeon, Sarah K.; Goodfellow, Marc
Department
Abstract
Psoriasis is a chronic inflammatory skin disease clinically characterized by the appearance of red colored, well-demarcated plaques with thickened skin and with silvery scales. Recent studies have established the involvement of a complex signalling network of interactions between cytokines, immune cells and skin cells called keratinocytes. Keratinocytes form the cells of the outermost layer of the skin (epidermis). Visible plaques in psoriasis are developed due to the fast proliferation and unusual differentiation of keratinocyte cells. Despite that, the exact mechanism of the appearance of these plaques in the cytokine-immune cell network is not clear. A mathematical model embodying interactions between key immune cells believed to be involved in psoriasis, keratinocytes and relevant cytokines has been developed. The complex network formed of these interactions poses several challenges. Here, we choose to study subnetworks of this complex network and initially focus on interactions involving TNFα, IL-23/IL-17, and IL-15. These are chosen based on known evidence of their therapeutic efficacy. In addition, we explore the role of IL-15 in the pathogenesis of psoriasis and its potential as a future drug target for a novel treatment option. We perform steady state analyses for these subnetworks and demonstrate that the interactions between cells, driven by cytokines could cause the emergence of a psoriasis state (hyper-proliferation of keratinocytes) when levels of TNFα, IL-23/IL-17 or IL-15 are increased. The model results explain and support the clinical potentiality of anti-cytokine treatments. Interestingly, our results suggest different dynamic scenarios underpin the pathogenesis of psoriasis, depending upon the dominant cytokines of subnetworks. We observed that the increase in the level of IL-23/IL-17 and IL-15 could lead to psoriasis via a bistable route, whereas an increase in the level of TNFα would lead to a monotonic and gradual disease progression. Further, we demonstrate how this insight, bistability, could be exploited to improve the current therapies and develop novel treatment strategies for psoriasis.
Publishing Year
Date Published
2021-01-26
Journal Title
Scientific Reports
Acknowledgement
RP acknowledges the Department of Science and Technology, India for the support through the DST-INSPIRE Faculty Award (DST/INSPIRE/04/2015/001939). This work was supported by the Engineering and Physical Sciences Research Council (EPSRC), United Kingdom (Grant numbers EP/J018295/1, EP/J018392/1, EP/N014391/1). The contribution of RP was also supported by the later Grant. This work was generously supported by the Welcome Trust Institutional Strategic Support Award (204909/Z/16/Z) too. The contribution of MG was supported by the EPSRC via EP/N014391/1 and a Wellcome Trust Institutional Strategic Support Award (WT105618MA). The contribution of YA was generously supported by the Wellcome Trust Institutional Strategic Support Award (WT105618MA).
Volume
11
Article Number
2204
eISSN
IST-REx-ID

Cite this

Pandey R, Al-Nuaimi Y, Mishra RK, Spurgeon SK, Goodfellow M. Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis. Scientific Reports. 2021;11. doi:10.1038/s41598-020-80507-7
Pandey, R., Al-Nuaimi, Y., Mishra, R. K., Spurgeon, S. K., & Goodfellow, M. (2021). Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis. Scientific Reports. Springer Nature. https://doi.org/10.1038/s41598-020-80507-7
Pandey, Rakesh, Yusur Al-Nuaimi, Rajiv Kumar Mishra, Sarah K. Spurgeon, and Marc Goodfellow. “Role of Subnetworks Mediated by TNF α, IL-23/IL-17 and IL-15 in a Network Involved in the Pathogenesis of Psoriasis.” Scientific Reports. Springer Nature, 2021. https://doi.org/10.1038/s41598-020-80507-7.
R. Pandey, Y. Al-Nuaimi, R. K. Mishra, S. K. Spurgeon, and M. Goodfellow, “Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis,” Scientific Reports, vol. 11. Springer Nature, 2021.
Pandey R, Al-Nuaimi Y, Mishra RK, Spurgeon SK, Goodfellow M. 2021. Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved in the pathogenesis of psoriasis. Scientific Reports. 11, 2204.
Pandey, Rakesh, et al. “Role of Subnetworks Mediated by TNF α, IL-23/IL-17 and IL-15 in a Network Involved in the Pathogenesis of Psoriasis.” Scientific Reports, vol. 11, 2204, Springer Nature, 2021, doi:10.1038/s41598-020-80507-7.
All files available under the following license(s):
Creative Commons Attribution 4.0 International Public License (CC-BY 4.0):
Main File(s)
Access Level
OA Open Access
Date Uploaded
2021-02-09
MD5 Checksum
e8a68df48750712671f5c47b0228e531


Export

Marked Publications

Open Data IST Research Explorer

Search this title in

Google Scholar