Mathematical Modeling Study Highlights Cytokine Balance and Stem Cell Feedback in Psoriasis Control
A new systems biology study using mathematical modeling provides insight into how cytokine imbalance drives psoriasis flares and suggests that restoring immune-epidermal feedback, rather than targeting single inflammatory pathways alone, may be key to achieving sustained disease control.
Investigators developed a dynamic model incorporating epidermal stem-cell differentiation, activated T cells and dendritic cells, keratinocytes, and a core cytokine network, including tumor necrosis factor (TNF), IL-23, IL-17, TGF-β, and IL-10. The model accounted for bidirectional interactions between immune cells, cytokines, and keratinocyte growth, allowing simulation of both stable disease states and flare-like dynamics.
Sensitivity analyses identified parameters most strongly influencing keratinocyte proliferation. In particular, increased TNF-driven keratinocyte upregulation and reduced IL-10 production by stem cells destabilized the system. Using Hopf bifurcation analysis, the authors showed that “higher TNF-driven keratinocyte up-regulation or lower IL-10 feedback induces oscillatory, flare-like dynamics,” while enhanced IL-10 signaling promoted stability and immune homeostasis.
The study also modeled therapeutic interventions. TNF inhibition, simulated as an impulsive control, reduced inflammation but failed to provide durable control. “TNF inhibition gives only temporary benefit,” the authors reported, reflecting rebound dynamics once inflammatory pressure resumed. In contrast, simulated stem cell infusion produced sustained suppression of immune activation and keratinocyte overgrowth by strengthening anti-inflammatory feedback loops.
According to the authors, these findings “highlight the importance of cytokine balance” and support stem cell-based strategies as a potential means of restoring long-term immune-epidermal homeostasis. By stabilizing IL-10–mediated regulation, stem cell approaches shifted the system toward a stable equilibrium rather than recurrent inflammatory oscillations.
For dermatologists, the key takeaway is conceptual rather than immediately practice changing. While biologics targeting TNF, IL-17, or IL-23 remain highly effective, this modeling study underscores why monotherapy interruption or partial suppression can allow disease recurrence. It also provides a theoretical framework supporting emerging regenerative or immune-modulating strategies aimed at rebalancing, rather than simply blocking, inflammatory pathways.
Although highly abstract and not a clinical trial, the work offers a mechanistic lens through which to understand psoriasis chronicity and flare behavior, and it points toward future therapies designed to stabilize immune regulation rather than suppress individual cytokines alone.
Reference
Kushary S, Ghosh T, Roy PK. Impulsive stem cell transplantation to modulate psoriasis: insights of complex cytokine network. Math Biosci. Published online January 18, 2026. doi:10.1016/j.mbs.2026.109623
