Heat shock proteins in the therapy of autoimmune diseases: too simple to be true?

Autoimmune diseases are characterized by the loss of immune tolerance to self-antigens which leads to an excessive immune responses and chronic inflammation. Although much progress has been made in revealing key players in pathophysiology of various autoimmune diseases, their therapy remains challenging and consists of conventional immunosuppressive treatments, including corticosteroids and more advanced biological therapies which are targeted at molecules involved in maintaining chronic inflammation. These therapies are focused on suppressing inflammation; nevertheless, a permanent balance between protective and pathogenic immune responses is not achieved. In addition, most of currently available therapies for autoimmune diseases induce severe side effects. Consequently, more effective and safer therapies are still required to control autoimmunity. Stress-induced cell protecting heat shock proteins (HSP) have been considered as a potential treatment targets for autoimmune diseases. HSP, predominantly intracellular components, might be released from bacteria or mammalian tissues and activate immune response. This activation may lead to either production of (auto)antibodies against HSP and/or induction of immune regulatory mechanisms, including expansion of desired T regulatory (Treg) cells. Because inadequate frequency or activity of Treg is a characteristic feature of autoimmune diseases, targeting this cell population is an important focus of immunotherapy approaches in autoimmunity.