2009 Stocki and Dickinson 2012 van Herwijnen et al. While interactions between bacterial- or self-HSP and host immune system components lead to stimulation of humoral (auto)immune response and the production of anti-HSP, numerous basic and preclinical studies revealed immunosuppressive activity of some HSP (van Eden et al. Therefore, self-Hsp60 epitopes may serve as altered peptide ligands (APLs) used for therapeutic purpose (Kim et al. Interestingly, only highly conserved Hsp60-derived epitopes used for animal immunization were disease-regulating in murine model of arthritis and self-Hsp60-reactive T cells displayed anergic phenotype with immunosuppressive potency. This has been confirmed in several murine models of autoimmune arthritis resembling rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) in human. For instance, immunoreactivity to Hsp60 chaperone is predominantly aimed at suppression of immune response. Both bacterial and autologous HSP are highly immunogenic in nature, and the immune response to these proteins has been observed in various inflammatory and autoimmune diseases. In addition, since various HSP are overexpressed in inflamed tissues and their presence in the extracellular space has been associated with the inflammation process, HSP became the focus of interest of scientists in the context of the autoimmune process. Intracellularly expressed mammalian HSP are widely studied molecular chaperones in essential cellular processes like polypeptide folding and translocation as well as native protein stabilization upon either physiological or pathological conditions. Based on molecular weight, HSP are categorized into several chaperone classes, including Hsp100, Hsp90, Hsp70, Hsp60, Hsp40, and the small HSP (Kampinga et al. They are localized in the cytoplasm and various organelles where they act as chaperones or proteases. 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.Įvolutionarily conserved heat shock proteins (HSP) are constitutively expressed and/or stress-induced cellular molecules. 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. HSP, predominantly intracellular components, might be released from bacteria or mammalian tissues and activate immune response. Stress-induced cell protecting heat shock proteins (HSP) have been considered as a potential treatment targets for autoimmune diseases. Consequently, more effective and safer therapies are still required to control autoimmunity. In addition, most of currently available therapies for autoimmune diseases induce severe side effects. These therapies are focused on suppressing inflammation nevertheless, a permanent balance between protective and pathogenic immune responses is not achieved. 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. Autoimmune diseases are characterized by the loss of immune tolerance to self-antigens which leads to an excessive immune responses and chronic inflammation.
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