Inflammation is part of many common diseases including autoimmune diseases, infections, but also cancer, obesity or even Alzheimer's disease. Macrophages are a major cell type involved in inflammation. Transcriptional programming is at the heart of macrophage activation and differentiation. Based on classical approaches we have learned a lot about macrophage activation, polarization, and macrophage function during the last decades, yet our understanding of the complex network of transcriptional programming regulating these processes remains unresolved. We have recently established a large transcriptome dataset of human macrophages stimulated with a diverse set of activation signals. Using a series of bioinformatical approaches, we were able to extend the current M1 versus M2-polarization model to a spectrum model of macrophage activation. In principle, macrophages compute every input signal to a very specific effector program. We are now applying this information to macrophage biology in inflammatory situations to determine novel human macrophage biology. E.g., we have already been able to reveal an unexpected loss of inflammatory signatures in patients with chronic obstructive pulmonary disease. This systematic approach will form the basis for the development of novel diagnostics and therapeutics targeting inflammation.
Disclosure of Interest None declared
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