Role of mitochondria in the development of autoinflammatory diseases

Abstract

Autoinflammatory diseases are hereditary inflammatory syndromes, which are characterized by unprovoked high activation of the innate immune response. The myeloid effector cells and the germline-encoded receptors of the innate immune system are implicated in the development of these diseases. Furthermore, in some autoinflammatory diseases the deregulated production of the proinflammatory cytokine IL-1β is reported. The processing of IL-1β requires the assembly of a macromolecular complex, the NLPR3 inflammasome. This complex activates caspase-1, which therefore cleaves the precursor of IL-1β. Compelling evidence shows the association of NLPR3 inflammasome activation with mitochondria. Increasing experimental evidence supports that the mitochondria regulate the innate immune response and they modulate inflammasome activation. Recent data also demonstrate that the impairment of mitochondrial integrity and homeostasis, accompanied by up-regulated production of ROS seems to be also involved in autoinflammatory diseases, such as TRAPS. The aim of the present thesis is to examine thoroughly all the research provided and try to shed light on the underlying mechanism by which mitochondria could induce the development of autoinflammatory syndromes.