While research has provided an enormous body of knowledge about the regulatory mechanisms behind chronic inflammation, it is difficult to assess the contribution of each individual process with current biological methods. In particular, what are the critical components and conditions triggering a change towards chronic inflammation, despite the multi-faceted mechanisms that promote immune tolerance? Furthermore, can we develop a rationale for improved strategies of therapeutic intervention? Currently available drugs targeting immune cell communication (so-called targeted or “biological” therapies), such as TNF-alpha blockers, often show limited effectiveness and considerable adverse effects. The goal of our group is to develop an interdisciplinary framework for dissecting and rationalizing intercellular communication networks, to investigate the effects of perturbations and thus pave the road for optimization of targeted therapies in the future.