Phosphorylation-Mediated IFN-γR2 Membrane Translocation Is Required to Activate Macrophage Innate Response
Authors: Xiaoqing Xu
Yan Gu
Kai Zhao
Xingguang Liu
Jia Xu
Ye Hu
Qian Zhang
Jiacheng Wu
Yanmei Han
Xuetao Cao
Juan Liu
Bing Liu
Journal: Cell (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: BTK; E-selectin; EFhd2; IFN-γR2; innate immunity
Affiliations: Department of Immunology and Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, 100005 Beijing, China; National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, 200433 Shanghai, China., Department of Immunology and Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, 100005 Beijing, China., National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, 200433 Shanghai, China., Translational Medicine Center, Academy of Military Medical Sciences, 100024 Beijing, China., Department of Immunology and Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, 100005 Beijing, China; National Key Laboratory of Medical Immunology and Institute of Immunology, Second Military Medical University, 200433 Shanghai, China; College of Life Science, Nankai University, 300071 Tianjin, China. Electronic address: .

Abstract:  As a critical step during innate response, the cytoplasmic β subunit (IFN-γR2) of interferon-γ receptor (IFN-γR) is induced and translocates to plasma membrane to join α subunit to form functional IFN-γR to mediate IFN-γ signaling. However, the mechanism driving membrane translocation and its significance remain largely unknown. We found, unexpectedly, that mice deficient in E-selectin, an endothelial cell-specific adhesion molecule, displayed impaired innate activation of macrophages upon Listeria monocytogenes infection yet had increased circulating IFN-γ. Inflammatory macrophages from E-selectin-deficient mice had less surface IFN-γR2 and impaired IFN-γ signaling. BTK elicited by extrinsic E-selectin engagement phosphorylates cytoplasmic IFN-γR2, facilitating EFhd2 binding and promoting IFN-γR2 trafficking from Golgi to cell membrane. Our findings demonstrate that membrane translocation of cytoplasmic IFN-γR2 is required to activate macrophage innate response against intracellular bacterial infection, identifying the assembly of functional cytokine receptors on cell membrane as an important layer in innate activation and cytokine signaling. 

Retracted: No

PubPeer comments:
 Figure 4E. The top two panels look more similar than expected. They are not identical, though, and the gated percentages are different. ![file] , 
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 The top panels actually are different for me. If you look at the two red rectangle frames carefully, you will find the difference: there are less spots close to the frame in the right one than the left. , 
 #3 Sigh. There are two trivial ways to change the number of spots in two FACS plots generated from the same dataset. One way is simply to cut and paste in more spots! The other way is to change the gating on the dataset so that the plotted cells are not 100% the same. The probability for most of the cells being in identical positions by chance probably canu2019t be calculated to a meaningful value. There are some interesting Shanghaied ImmunoBlots (SIBs) in Fig. 5. For starters, I draw your attention to p-ERK1 2 in Fig. 5A. Not only do the lower bands in the left slice have a different shape from the upper bands, as well as from the equivalent ERK bands in the reprobed lower slice, they are also marked by straight white lines, implying how they were pasted in ![image] , 
 ![file] By adjusting the contrast of the pointed figure, the bg is obviously different. If this is copy and paste, will the background change? With my eyes, they are almost identical to me and i cannot understand how this could happen. Under no circumstance, two flows would have same dot pattern, even run the same sample twice. I think the only way can answer this question is to upload the original FCS files, try if we can see same or similar pattern from separated FCS files. , 
 #5  By adjusting the contrast of the pointed figure, the bg is obviously different. If this is copy and paste, will the background change? What you are seeing there are JPG image-compression artefacts, though. Below, points cells present in the left-hand panel but not the right-hand one appear as blue. The rest cancel out. ![file] , 
 Correction, 4 March 2021: https: www.cell.com cell fulltext S0092-8674(20)30214-2  *During preparation of the figures of this paper, we made an error in the upper right panel of Figure 4E. This panel shows the quantitative analysis of membrane IFN-u03b3R2+ peritoneal macrophages from HSC transplanted mice prior to the infection with Listeria monocytogenes. The flow cytometry output (FCS file) in the upper right panel was accidentally duplicated from the FCS file of the upper left panel. However, the gating applied in the processing of the data was different, resulting in different gated percentage. Hence, the data in this (upper right) panel are incorrect and the corrected version of Figure 4E shown here includes the correct CD45.1 WT HSCu2192Seleu2212 u2212 at time point of day 0. We apologize for the error and for any inconvenience that they may have caused.* ,