Research ArticleLung Disease

The proinflammatory role of HECTD2 in innate immunity and experimental lung injury

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Science Translational Medicine  08 Jul 2015:
Vol. 7, Issue 295, pp. 295ra109
DOI: 10.1126/scitranslmed.aab3881

Calming the cytokine storm

The innate immune response is poised to act quickly in the face of pathogenic invaders; however, this priming may lead to a cytokine storm, where excessive production of proinflammatory cytokines harms the host. Coon et al. now report that HECTD2, a ubiquitin E3 ligase, can degrade the anti-inflammatory protein PIAS1, increasing this inflammatory effect. Indeed, a small-molecule inhibitor of HECTD2 reduced lung inflammation in a mouse model. Moreover, people with a polymorphism in HECTD2 had lower inflammation and were protected from acute respiratory distress syndrome. Thus, HECTD2 serves as a new therapeutic target for inflammation-induced lung injury.