Figure 1.

Hypothesis: exploitation of IL-10 and IL-22 signaling by type I IFN. Under “basal” conditions signal transduction of IL-10 (A) and IL-22 (B) is dominated by activation of STAT3 in responsive cells types. Those are primarily mononuclear phagocytes/DC or cells of epithelial origin for IL-10 or IL-22, respectively. In this mode, IL-10 will lead to cellular deactivation mediating a pronounced anti-inflammatory tissue response. Although mechanistic details are still cloudy, temporally prolonged STAT3 activation is pivotal for this regulatory path. Experimental data suggest direct or indirect inhibition of NF-κB as one mode of STAT3 action which connects to downregulation of key pro-inflammatory cytokines and effector molecules. STAT3 activation by IL-22 facilitates proliferation and anti-apoptosis in epithelial cells. Both of these processes would obviously favor tissue repair but likewise tumor growth. Upon cellular priming by type I IFN, IL-10, and IL-22 signaling is targeted toward surplus STAT1 activation (Sharif et al., 2004; Bachmann et al., 2012) which, in contrast to STAT3, would support Th1-like inflammation and processes that favor apoptosis and control of tumor growth. Notably, amplification of Th1-like inflammation may further enhance anti-bacterial properties of IL-22 at host/environment interfaces.