Impulsive stem cell transplantation to modulate psoriasis: Insights of complex cytokine network

Psoriasis is caused by abnormal interactions between immune cells, cytokines, and keratinocytes. In this study, we develop a dynamical model that includes epidermal stem-cell differentiation, activated T cells, activated dendritic cells, keratinocytes, and a selected cytokine network (TNF, TGF-β, IL-23, IL-17, IL-10). The model considers two-way interactions between cytokines and cells, and the quasi-steady-state approximation is applied to reduce complexity. We determine the invariant region that ensures bounded solutions and analyze the local stability of the interior equilibrium. Sensitivity analysis shows key parameters that strongly influence keratinocyte growth. Hopf bifurcation analysis with respect to TNF-driven keratinocyte up-regulation (ζ₃) and IL-10 production by stem cells (p₇) reveals that higher ζ₃ or lower p₇ induce oscillatory, flare-like dynamics, while stronger IL-10 feedback stabilizes the system. Numerical simulations test therapeutic strategies, including TNF inhibition and stem cell infusion, modeled with impulsive control. The mathematical results show conditions under which impulsive periodic orbits become stable. Simulations indicate that TNF inhibition gives only temporary benefit, whereas stem cell infusion provides sustained control of immune activation and keratinocyte overgrowth. Overall, the study highlights the importance of cytokine balance and supports stem cell therapy as a promising approach for restoring immune-epidermal homeostasis in psoriasis.