Research ArticleImmunology

Human IL-22 binding protein isoforms act as a rheostat for IL-22 signaling

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Science Signaling  27 Sep 2016:
Vol. 9, Issue 447, pp. ra95
DOI: 10.1126/scisignal.aad9887

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IL-22 signaling complexity

Dysregulated signaling by the cytokine interleukin-22 (IL-22) results in inflammatory disease, and inhibitors of IL-22 are in clinical trials for the treatment of psoriasis and rheumatoid arthritis. However, IL-22 already has natural inhibitors in the form of IL-22 binding proteins (IL-22BPs), which are soluble, receptor-like proteins that bind to IL-22 and prevent it from binding its receptors on target cells. Lim et al. characterized the three IL-22BP isoforms of humans. One isoform was not secreted and so failed to antagonize IL-22 signaling. Compared with IL-22BPi3, IL-22BPi2 was more potent when tested in binding assays but less abundant in undamaged and noninfected tissues. However, IL-22BPi2 was the only isoform that was increased in abundance in response to inflammatory stimuli. Together, these data suggest that IL-22BPi3 and IL-22BPi2 serve as constitutive and inducible limiters, respectively, of inflammatory signaling mediated by IL-22. Aberrant regulation of this IL-22BP rheostat could contribute to inflammatory disease or prevent appropriate responses to injury or infection in target tissues.

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