Interferon-γ （IFN-γ） triggers macrophage for inflammation response by activating the intracellular JAK-STAT1 signaling. Suppressor of cytokine signaling 1 （SOCS1） and protein tyrosine phosphatases can negatively...Interferon-γ （IFN-γ） triggers macrophage for inflammation response by activating the intracellular JAK-STAT1 signaling. Suppressor of cytokine signaling 1 （SOCS1） and protein tyrosine phosphatases can negatively modulate IFN-γ signaling. Here, we identify a novel negative feedback loop mediated by STAT3-SOCS3, which is tightly controlled by SENP1 via de-SUMOylation of protein tyrosine phosphatase 1B （PTPIB）, in IFN-y signaling. SENP1-deficient macrophages show defects in IFN-γ signaling and M1 macrophage activation. PTP1B in SENP1-deficient macrophages is highly SUMOylated, which reduces PTP1B-induced de-phosphorylation of STAT3. Activated STAT3 then suppresses STAT1 activation via SOCS3 induction in SENP1-deficient macro- phages. Accordingly, SENP1-deficient macrophages show reduced ability to resist Listerio rnonocytogenes infection. These results reveal a crucial role of SENP1-controlled STAT1 and STAT3 balance in rnacrophage polarization.展开更多
文摘Interferon-γ （IFN-γ） triggers macrophage for inflammation response by activating the intracellular JAK-STAT1 signaling. Suppressor of cytokine signaling 1 （SOCS1） and protein tyrosine phosphatases can negatively modulate IFN-γ signaling. Here, we identify a novel negative feedback loop mediated by STAT3-SOCS3, which is tightly controlled by SENP1 via de-SUMOylation of protein tyrosine phosphatase 1B （PTPIB）, in IFN-y signaling. SENP1-deficient macrophages show defects in IFN-γ signaling and M1 macrophage activation. PTP1B in SENP1-deficient macrophages is highly SUMOylated, which reduces PTP1B-induced de-phosphorylation of STAT3. Activated STAT3 then suppresses STAT1 activation via SOCS3 induction in SENP1-deficient macro- phages. Accordingly, SENP1-deficient macrophages show reduced ability to resist Listerio rnonocytogenes infection. These results reveal a crucial role of SENP1-controlled STAT1 and STAT3 balance in rnacrophage polarization.
