---
_id: '9097'
abstract:
- lang: eng
text: 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.
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).
article_number: '2204'
article_processing_charge: No
article_type: original
author:
- first_name: Rakesh
full_name: Pandey, Rakesh
last_name: Pandey
- first_name: Yusur
full_name: Al-Nuaimi, Yusur
last_name: Al-Nuaimi
- first_name: Rajiv Kumar
full_name: Mishra, Rajiv Kumar
id: 46CB58F2-F248-11E8-B48F-1D18A9856A87
last_name: Mishra
- first_name: Sarah K.
full_name: Spurgeon, Sarah K.
last_name: Spurgeon
- first_name: Marc
full_name: Goodfellow, Marc
last_name: Goodfellow
citation:
ama: 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
apa: 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
chicago: 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.
ieee: 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.
ista: 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.
mla: 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.
short: R. Pandey, Y. Al-Nuaimi, R.K. Mishra, S.K. Spurgeon, M. Goodfellow, Scientific
Reports 11 (2021).
date_created: 2021-02-07T23:01:12Z
date_published: 2021-01-26T00:00:00Z
date_updated: 2022-08-19T07:22:23Z
day: '26'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1038/s41598-020-80507-7
file:
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checksum: e8a68df48750712671f5c47b0228e531
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creator: dernst
date_created: 2021-02-09T07:33:23Z
date_updated: 2021-02-09T07:33:23Z
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file_name: 2021_ScientificReports_Pandey.pdf
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success: 1
file_date_updated: 2021-02-09T07:33:23Z
has_accepted_license: '1'
intvolume: ' 11'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '01'
oa: 1
oa_version: Published Version
publication: Scientific Reports
publication_identifier:
eissn:
- '20452322'
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Role of subnetworks mediated by TNF α, IL-23/IL-17 and IL-15 in a network involved
in the pathogenesis of psoriasis
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 11
year: '2021'
...