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Innate immunity-induced IRF3 signaling suppress TGF-β via Smad

 

Transforming growth factor β (TGF-β) signaling is a central regulator of many process, including immune responses and cancer progression. By investigating the innate host defense, Xu et al. found RIG-I-Like receptor (RLR) signaling suppress TGF-β via activation of Interferon regulatory factor 3 (IRF3). The article was published on Molecular Cell, recently.

 

Most of the cells perform non-specific innate host defense to quickly recognize pathogens and start a series of defensive activities. RLRs can bind to viral double-stranded RNA (dsRNA) and indirectly activate the signaling mediator IRF3. Researchers found IRF3 suppress TGF-β responses in two ways: 1) by competing with TGF-β on binding to Smad3, IRF3 inhibit TGF-β signaling that transfer through Smad3 in the cell plasma; 2) interfere the interaction between functional Smad3 transcription complexes and the coregulators in the nucleus. The findings indicate a crosstalk between IRF3 mediated innate defense and Smad mediated TGF-β signaling. The repression of TGF-β was proved to inhibit epithelial-mesenchymal transition (EMT) and differentiation of Treg cells, in addition, may potently affect cancer development and progression as well as the modulation of immune responses.

 

Reference:
Mol Cell. 2014 Dec 18;56(6):723-37.

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TGF-beta/Smad IκB/IKK