Research ArticleImmunology

A CC′ Loop Decoy Peptide Blocks the Interaction Between Act1 and IL-17RA to Attenuate IL-17– and IL-25–Induced Inflammation

Sci. Signal.  01 Nov 2011:
Vol. 4, Issue 197, pp. ra72
DOI: 10.1126/scisignal.2001843

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Quelling Inflammation with a Peptide

Members of the interleukin-17 (IL-17) family of cytokines, including IL-17A and IL-25, are implicated in the pathogenesis of various inflammatory conditions, including allergen-induced pulmonary inflammation. Indeed, the concentrations of IL-17A and IL-25 are higher in the lungs of asthmatic patients than in those of unaffected individuals. IL-17A and IL-25 share a common receptor subunit, IL-17RA, to which is recruited the adaptor protein Act1 through interactions between its SEFIR domain and the SEFIR domain of the receptor. Liu et al. identified the CC′ loop region within the SEFIR domain of Act1 as critical for receptor-adaptor protein interactions. A cell-permeable peptide based on this region inhibited IL-17– and IL-25–dependent signaling in vitro and reduced disease in a mouse model of pulmonary inflammation, suggesting that such a strategy may provide therapies to treat IL-17–mediated inflammatory diseases in humans.