Interstitial lung disease and the STING pathway
Prasad Palani Velu, Gaofeng Zhu, Karen J. Mackenzie
Prasad Palani Velu, Gaofeng Zhu, Karen J. Mackenzie
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Interstitial lung disease and the STING pathway

Abstract

Identification of the genetic mutations underlying the ultrarare monogenic conditions STING-associated vasculopathy with onset in infancy (SAVI) and coatomer protein complex subunit alpha (COPA) syndrome revealed a role for the stimulator of interferon genes (STING) immune pathway in the pathogenesis of interstitial lung disease (ILD) in these conditions. STING-focused therapeutics could be a potential avenue for the treatment of SAVI and COPA syndrome in the future, yet the relevance of STING to more common types of ILD is not clear. Here, we provide an overview of SAVI and COPA syndrome, the nature of ILD in these conditions, and current evidence regarding STING activity in their pathogenesis. We discuss data from studies of a variety of other ILDs and model systems and explore the potential role for STING in more common forms of ILD.

Authors

Prasad Palani Velu, Gaofeng Zhu, Karen J. Mackenzie

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Figure 3

Potential outcomes of STING pathway activation.

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Potential outcomes of STING pathway activation. The varied consequences ...
The varied consequences of STING pathway activation continue to be ascertained. In addition to its prominent role in the production of IFN-I and other proinflammatory mediators, STING activation has also been shown to have roles in inducing cell death, autophagy, and senescence responses. Biological outcomes are likely to vary depending on the nature of STING activation, and this remains an active area of study. Here, we postulate that some outcomes from STING signaling could be more pertinent to types of ILD that have strong fibrotic components compared with ILDs where robust inflammatory phenotypes are more evident. However, interplay between the different outcomes of STING signaling is likely, and the role of inflammation and fibrosis in some ILDs may also be indistinct. Important questions for future research are highlighted. SASP, senescence-associated secretory phenotype.