Chapter 8: Clusterin: A multifacet protein at the crossroad of inflammation and autoimmunity.

For years, clusterin has been recognized as a secreted protein and a large number of works demonstrated that this ubiquitously expressed protein has multiple activities. Among the described activities several were related to inflammation and immunity such as its regulatory activity on complement. Then it became clear that a nuclear form of the protein with proapoptotic property existed and more recently that a cytoplasmic form could regulate NF-kappaB pathway. Again, these activities have a strong repercussion in inflammation and immunity. On the other hand, data available on the exact role of CLU in these processes and autoimmunity were quite scarce until recently. Indeed, in the last few years, a differential CLU expression in subtype of T cells, the regulation of CLU expression by proinflammatory cytokines and molecules, the regulation of expression and function of CLU depending on its subcellular localization, the interaction of CLU with nuclear and intracellular proteins were all reported. Adding these new roles of CLU to the already reported functions of this protein allows a better understanding of its role and potential involvement in several inflammatory and immunological processes and, in particular, autoimmunity. In this sense, rheumatoid arthritis appears to be a very attractive disease to build a new paradigm of the role and function of CLU because it makes the link between proliferation, inflammation, and autoimmunity. We will try to see in this review how to bring altogether the old and new knowledge on CLU with inflammation and autoimmunity. Nevertheless, it is clear that CLU has not yet revealed all its secrets in inflammation and autoimmunity.