Yu, TingtingZuo, YongCai, RongHuang, XianWu, ShuaiZhang, ChenxiChin, Y. EugeneLi, DongdongZhang, ZhenningXia, NansongWang, QiShen, HaoYao, XuebiaoZhang, Zhong-YinXue, SongShen, LeiCheng, Jinke2018-01-182018-01-182017-04Yu, T., Zuo, Y., Cai, R., Huang, X., Wu, S., Zhang, C., … Cheng, J. (2017). SENP1 regulates IFN-γ−STAT1 signaling through STAT3−SOCS3 negative feedback loop. Journal of Molecular Cell Biology, 9(2), 144–153. https://doi.org/10.1093/jmcb/mjw042https://hdl.handle.net/1805/15031Interferon-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 (PTP1B), in IFN-γ 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 macrophages. Accordingly, SENP1-deficient macrophages show reduced ability to resist Listeria monocytogenes infection. These results reveal a crucial role of SENP1-controlled STAT1 and STAT3 balance in macrophage polarization.enPublisher PolicyIFN-γmacrophageSENP1Article