Research ArticleImmunology

Loss of epithelial Gq and G11 signaling inhibits TGFβ production but promotes IL-33–mediated macrophage polarization and emphysema

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Science Signaling  25 Oct 2016:
Vol. 9, Issue 451, pp. ra104
DOI: 10.1126/scisignal.aad5568

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Gq/11 signaling maintains healthy lungs

Loss of signaling by the cytokine transforming growth factor–β (TGFβ) in mice results in emphysema-like symptoms, whereas excessive TGFβ signaling results in pulmonary fibrosis and ventilator-associated lung injury. G proteins of the Gq/11 and G12/13 families mediate the integrin-dependent activation and release of latent TGFβ from the epithelial cells. John et al. found that mice deficient in Gq/11, but not those deficient in G12/13, in lung epithelial cells had defective TGFβ activation and emphysema-like symptoms. In addition, the Gq/11-deficient mice had lung inflammation associated with increased amounts of the cytokine IL-33. However, the mice were protected from ventilator-induced injury. Together, these data suggest that Gq/11 signaling is required for optimal TGFβ activation in the lung and the prevention of inflammation.

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