Pharmacological regulators of autophagy and their link with modulators of lupus disease

Autophagy is a central regulator of cell survival. It displays both anti- and pro-death roles that are decisive in the maintenance of cell homeostasis. Initially described in several eukaryotic cellular models as being induced under nutrient stress favouring survival by energy supply, autophagy was found later to display other decisive physiological roles, especially in the immune system. Thus, it is involved in antigen presentation and lymphocyte differentiation as well as in the balance regulating survival/death and activation of lymphocytes. Autophagy therefore appears to be central in the regulation of inflammation. The observation that autophagy is deregulated in systemic lupus erythematosus is recent. This discovery revives the programme dealing with the design and development of pharmacological autophagy regulators in the therapeutic context of lupus, a debilitating autoimmune disease that affects several million people in the world. A large number of molecules that positively and negatively regulate autophagy have been described, most of them with therapeutic indications in cancer and infection. Only a few, however, are effectively potent activators or inhibitors endowed with experimentally demonstrated selective properties. In this review article, we highlight the most relevant ones and summarize what we know regarding their mechanism of action. We emphasize the link between pharmacological regulators of autophagy and inducers or inhibitors of lupus disease and discuss the fundamental and pharmacological/therapeutic interest of this functional interplay.