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Cytokines

ISG15 — human deficiency reveals new proficiency

Nature Reviews Immunology volume 14, pages 780–781 (2014)Cite this article

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a novel role for ISG15 in suppressing the type I IFN response

First, the lack of a history of mycobacterial infection in the newly identified ISG15-deficient individuals was owing to the fact that they did not receive the Bacille Calmette–Guérin (BCG) vaccine that had triggered clinical disease in the previously studied patients. Although the previously identified ISG15-deficient individuals did not suffer from seizures, brain imaging revealed that both sets of patients had calcium deposits in their basal ganglia. As such pathology is characteristic of autoinflammatory interferonopathies, the authors hypothesized that enhanced type I IFN signalling may also underlie the ISG15-deficient phenotype. Indeed, peripheral blood samples from ISG15-deficient patients showed significantly increased mRNA-level expression of canonical type I IFN-stimulated genes (ISGs), which indicates an enhanced type I IFN response and is also consistent with their ability to control virus infection. These findings were replicated in studies using patient-derived fibroblasts, which also showed that the significant upregulation of IFN-induced transcripts was reversed when these cells were transduced with ISG15.

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References

  1. Zhang, X. et al. Human intracellular ISG15 prevents interferon-α/β over-amplification and auto-inflammation. Nature http://dx.doi.org/10.1038/nature13801 (2014)

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Authors
  1. Lydia Shipman
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Ivashkiv, L. B. & Donlin, L. T. Regulation of type I interferon responses. Nature Rev. Immunol. 14, 36–49 (2014)

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Shipman, L. ISG15 — human deficiency reveals new proficiency. Nat Rev Immunol 14, 780–781 (2014). https://doi.org/10.1038/nri3767

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