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Adv Exp Med Biol. 2012;946:223-35. doi: 10.1007/978-1-4614-0106-3_13.

Function of Act1 in IL-17 family signaling and autoimmunity.

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  • 1Department of Immunology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA. wul3@ccf.org


The maintenance of immune homeostasis requires the delicate balance between response to foreign antigens and tolerance to self. As such, when this balance is disrupted, immunodeficiency or autoimmunity may manifest. The adaptor molecule known as Act1 is a critical mediator of IL-17 receptor receptor family signaling. This chapter will detail the current understanding of Act1 's role in signal transduction as well as address the fundamental role of Act1 in autoimmunity. At the molecular level Act1 interacts with IL-17 R through the conserved SEFIR domain, binds TRAF proteins and exerts E3 ubiquitin ligase activity. In in vivo models, Act1 deficiency provides protection against experimental autoimmune diseases, such as colitis and EAE. Yet mice lacking in Act1 develop spontaneous autoimmune diseases. Indeed, the utility of Act1 seems to rely on the specific cell type expression that may determine the pathway that Act1 mediates.

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