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. 2017 Oct 23;18(10):2197. doi: 10.3390/ijms18102197

Figure 3.

Figure 3

MT-Zn axis in tolerogenic DC–Treg interactions. DCs exposed to a pool of extracellular Zn develop a tolerogenic phenotype. Zn imported into DCs triggers MT-1 expression, possibly in an MTF-1 dependent manner. MT1 is expressed on the membrane of tolerogenic DCs and may also be actively secreted and bind to the T cell membrane. Upon activation, T cells import Zn via ZIP6 that mobilizes to the DC-T cell synapse. Zn sequestration by extracellular MTs may hinder this process, potentially stalling T cell activation. However, MT expression within T cells suppresses Treg development. IL-27 induces Tregs (in this case, IL-10 producing Tr1 cells) via STAT1 and STAT3 signaling. These STATs induce MT1 and MT2 that negatively feedback to inhibit STAT activation. MTs plausibly sequester Zn from PTP1B, an enzyme that is inhibited by Zn. Active PTP1B mediates dephosphorylation of STAT1 and STAT3 ultimately attenuating Treg development. Red dots, Zn ions; all solid lines and arrows are known links; all dotted lines and arrows are predicted links; red T bar depicts inhibition of STAT1/3 by PTP1B (active).