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Modeling of the Network Mediated by IL-36 Involved inPsoriasis

Pandey, S.; Tiwari, S.; Basu, S.; Mishra, R. K.; Pandey, R.

2023-07-03 systems biology
10.1101/2023.07.03.547538 bioRxiv
Show abstract

Pathogenesis of inflammatory, chronic and common skin disease Psoriasis involves immune cells, skin cells (keratinocytes) and cytokines secreted by them. Hyperproliferation and abnormal differentiation of keratinocytes are believed to be a hallmark of it. Roles of several cytokines such as TNF, IL-15, IL-17 and IL-23 in Psoriasis have been explored through mathematical/computational models as well as experimentally. However, the role of pro-inflammatory cytokine IL-36 is still elusive, especially in the case of General Pustular Psoriasis, a prevalent type of Psoriasis. To explore the role of that here, we construct a network embodying indirect cell-cell interactions of a few immune and skin cells mediated by IL-36 based on the existing knowledge. Further, we develop a mathematical model for the network and study the steady-state behaviour of that. Our results demonstrate that an increase in the level of IL-36 could lead to the hyper-proliferation of keratinocytes and, thus, Psoriasis. In addition, the analysis suggests that the plaque formation and progression of Psoriasis could occur via a gradual or switch-like increase in the population of keratinocytes. The switch-like increase would be due to the bistable behaviour of the network and could be used as a novel treatment strategy, as proposed and demonstrated earlier.

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