Montaseri, G. | Search bioRxiv

bioRxiv2020

An adaptive control scheme for Interleukin-2 therapy

Regulatory T cells (Treg) are suppressor cells that control self-reactive and excessive effector conventional helper T cell (Tconv) responses. Breakdown of the balance between Tregs and Tconvs is a hallmark of autoimmune and inflammatory diseases. Due to the positive dependency of both populations on Interleukin-2 (IL-2), it is subtle leverage to restore the healthy immune balance. By employing a mechanistic mathematical model, we studied the IL-2 therapy in order to increase and stabilize Treg population and restrict inflammatory Tconv response. We introduced an adaptive control strategy to design the minimal IL-2 dosage. This adaptive strategy allows for an individualized therapy based on the feedback of immune kinetics of the patient. Our in silico results suggest that a minimal Treg population is required to restrict the transient side-effect of IL-2 injections on the effector Tconv response. The combination of IL-2 and adoptive Treg transfer therapies is able to limit this side effect in our simulations. Implications of our in silico results are discussed in the context of autoimmunity and transplantation.

immunology↗

bioRxiv2019

Mathematical model shows how sleep may affect amyloid β fibrillization

Deposition of amyloid {beta} (A{beta}) fibers in extra-cellular matrix of the brain is a ubiquitous feature associated with several neurodegenerative disorders, especially Alzheimers disease (AD). While many of the biological aspects that contribute to the formation of A{beta} plaques are well addressed at the intra- and inter-cellular level in short timescales, an understanding of how A{beta} fibrillization usually starts to dominate at a longer timescale in spite of the presence of mechanisms dedicated to A{beta} clearance, is still lacking. Furthermore, no existing mathematical model integrates the impact of diurnal neural activity as emanated from circadian regulation to predict disease progression due to a disruption in sleep-wake cycle. In this study, we develop a minimal model of A{beta} fibrillization to investigate the onset of AD over a long time-scale. Our results suggest that the diseased state is a manifestation of a phase change of the system from soluble A{beta} (sA{beta}) to fibrillar A{beta} (fA{beta}) domination upon surpassing a threshold in the production rate of soluble A{beta}. By incorporating the circadian rhythm into our model, we reveal that fA{beta} accumulation is crucially dependent on the regulation of sleep-wake cycle, thereby indicating the importance of a good sleep hygiene in averting AD onset. We also discuss potential intervention schemes to reduce fA{beta} accumulation in the brain by modification of the critical sA{beta} production rate.

systems biology↗