Pro-inflammatory and pathogenic properties of Annexin-A1: The whole is greater than the sum of its parts

Abstract According to Aristotle, “ The whole is greater than the sum of its parts ” and yet, although a long time has passed still, we seem to struggle to accept this universal concept. Searching in the literature for the biological function of Annexin-A1, one would find a wealth of information on its homeostatic and protective anti-inflammatory effects. However, very little has been said on its emerging role in a wide variety of pathological conditions ranging from cancer to autoimmunity. In this commentary, we will focus our attention on this novel pro-inflammatory and pathogenic “dark side” of Annexin-A1. We will summarize our current understanding of the signaling pathways regulated by this protein and link it to clinical and experimental evidences. Finally we will discuss assets and limitations of Annexin-A1 therapeutic strategies. Most importantly, we hope that this commentary will provide scientific support to “controversial” findings one might encounter while studying this fascinating protein.