A Role for the Cytoplasmic Adaptor Protein Act1 in Mediating IL-17 Signaling

Anders Lindén^*

Department of Internal Medicine/Respiratory Medicine and Allergology, Institute of Medicine, Sahlgrenska Academy at Göteborg University, Sweden.

Abstract: Interleukin (IL)–17 (also known as IL-17A) plays an important role in host defense and inflammatory disorders, in part by linking the activation of a subset of T lymphocytes to the mobilization of neutrophils and macrophages. IL-17 exerts its effects both directly and indirectly; the latter by stimulating the production of various chemokines, IL-6, and growth factors from resident cells in the affected tissue. As a result, IL-17 coordinates the innate immune response to extracellular bacteria, which is interesting because IL-17 is produced by several types of T cells that are traditionally regarded as key players in adaptive immunity. Studies have uncovered the function and relevance of a unique subset of CD4⁺ T helper (Th) cells that produce IL-17 (Th17 cells), but our understanding of the function of IL-17 receptors (IL-17Rs) and their downstream signaling pathways remains poor. This Review discusses studies that suggest that the cytoplasmic adaptor protein Act1 [nuclear factor-B (NF-B) activator 1] is essential for linking stimulation of IL-17Rs to downstream signaling pathways, and, therefore, that Act1 might play a role in local inflammatory responses. Act1 mediates activation of NF-B and the subsequent production of IL-6 and chemokines that are chemotactic for neutrophils and macrophages. These findings have increased our understanding of host defense against bacteria and indicated a role for Act1 in mediating in chronic inflammatory disease. Future studies on Act1 and IL-17 signaling should contribute to the identification and improved understanding of the mechanisms behind aberrant innate immune responses in chronic inflammatory disease.

*E-mail: anders.linden{at}gu.se

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In Science Signaling

EDITORIAL GUIDES
Immunology
Focus Issue: Uncovering Immunological Secrets

John F. Foley and Elizabeth M. Adler (7 August 2007)
Sci. STKE 2007 (398), eg7. [DOI: 10.1126/stke.3982007eg7]
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