Flare-Ups and Remission in Crohn’s Disease Using T-Cell Model Dynamics

Crohn's disease is a type of chronic inflammatory bowel disease that can involve states of remission and unpredictable flare-ups. These flare-ups can greatly affect health and the quality of a person's life. The change from remission to flare-up or vice versa are caused by complex interactions within the immune system. Specifically, this involves interactions between auto-reactive T cells, which are associated with inflammation, and regulatory T cells, which help keep immune responses under control. This paper created and used a mathematical model to analyze how the interactions between these two cell populations can result in different patterns of Crohn's disease activity. The model created for this paper employs a system of coupled differential equations. These equations are used to represent production, growth, suppression, and decay of the auto-reactive and regulatory T cells. In the model, auto-reactive T cells can amplify by themselves, while the regulatory T cells respond to auto-reactive immune system activity and suppress it if needed. The model also includes a stochastic noise term, which is added to represent unpredictable triggers of flare-up or uncontrollable environmental factors like diet, infections, stress and more. When the model was simulated, it showed four states of disease activity. These 4 were a persistent healthy state, regular oscillations between low and high inflammation, a persistent inflammatory state, and irregular flare-ups with remission periods in between. When flare-ups were occurring, random disturbances led to a temporary increase in the amount of auto-reactive T cells present. In response, regulatory T cell levels also went up in order to suppress the inflammation and send the system back down to normal. These results indicate that simple interactions between the two types of T cells can be adequate to explain the chronic and unpredictable activity of Crohn's disease. Lastly, the model shows that amplifying the auto-reactive T cells can be a possible treatment target. However, much more research will have to be conducted, and it will need to take into account other factors such as microbes, tissue damage, other immune cells, clinical data and more.