Tim-3 promotes intestinal homeostasis in DSS colitis by inhibiting M1 polarization of macrophages.

Abstract

Tim-3 is involved in the physiopathology of inflammatory bowel disease (IBD), but the underlying mechanism is unknown. Here, we demonstrated that, in mouse with DSS colitis, Tim-3 inhibited the polarization of pathogenic pro-inflammatory M1 macrophages, while Tim-3 downregulation or blockade resulted in an increased M1 response. Adoptive transfer of Tim-3-silenced macrophages worsened DSS colitis and enhanced inflammation, while Tim-3 overexpression attenuated DSS colitis by decreasing the M1 macrophage response. Co-culture of Tim-3-overexpressing macrophages with intestinal lymphocytes decreased the pro-inflammatory response. Tim-3 shaped intestinal macrophage polarization may be TLR-4 dependent since Tim-3 blockade failed to exacerbate colitis or increase M1 macrophage response in the TLR-4 KO model. Finally, Tim-3 signaling inhibited phosphorylation of IRF3, a TLR-4 downstream transcriptional factor regulating macrophage polarization. A better understanding of this pathway may shed new light on colitis pathogenesis and result in a new therapeutic strategy.

DOI: 10.1016/j.clim.2015.07.008
05010020162017
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@article{Jiang2015Tim3PI, title={Tim-3 promotes intestinal homeostasis in DSS colitis by inhibiting M1 polarization of macrophages.}, author={Xingwei Jiang and Jiahui Yu and Qingzhu Shi and Yan Xiao and Wei Wang and Guojiang Chen and Zhi Zhao and Renxi Wang and He Xiao and Chunmei Hou and Jiannan Feng and Yuan-fang Ma and Beifen Shen and Lili Wang and Yan Li and Gencheng Han}, journal={Clinical immunology}, year={2015}, volume={160 2}, pages={328-35} }