Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

This perspective outlines an approach to improve mechanistic understanding of macrophages in inflammation and tissue homeostasis, with a focus on human inflammatory bowel disease (IBD). The approach integrates wet-lab and in-silico experimentation, driven by mechanistic mathematical models of relevant biological processes. Although wet-lab experimentation with genetically modified mouse models and primary human cells and tissues have provided important insights, the role of macrophages in human IBD remains poorly understood. Key open questions include: (1) To what degree hyperinflammatory processes (e.g., gain of cytokine production) and immunodeficiency (e.g., loss of bacterial killing) intersect to drive IBD pathophysiology? and (2) What are the roles of macrophage heterogeneity in IBD onset and progression? Mathematical modeling offers a synergistic approach that can be used to address such questions. Mechanistic models are useful for informing wet-lab experimental designs and provide a knowledge constrained framework for quantitative analysis and interpretation of resulting experimental data. The majority of published mathematical models of macrophage function are based either on animal models, or immortalized human cell lines. These experimental models do not recapitulate important features of human gastrointestinal pathophysiology, and, therefore are limited in the extent to which they can fully inform understanding of human IBD. Thus, we envision a future where mechanistic mathematical models are based on features relevant to human disease and parametrized by richer human datasets, including biopsy tissues taken from IBD patients, human organ-on-a-chip systems and other high-throughput clinical data derived from experimental medicine studies and/or clinical trials on IBD patients.

Original publication




Journal article


Front Immunol

Publication Date





IBD, in silico experimentation, macrophages, mechanistic mathematical models, monocytes