title: TIGIT negatively regulates inflammation by altering macrophage phenotype.
abstract: Macrophages function as an essential component of innate immune system, contributing to both the initiation and appropriate resolution of inflammation. The exposure of macrophages to the microbial products, such as lipopolysaccharide (LPS), can strongly shift the balance between tissue homeostasis and inflammation in favor of causing systemic damage, in which macrophage M1 polarization play important roles. Strategies aiming at restoring the balance of macrophage polarization remain to be further explored. Herein, we have demonstrated that poliovirus receptor (PVR), the receptor of TIGIT, was dramatically upregulated on the surface of mouse peritoneal macrophages when exposed to LPS. TIGIT-Fc fusion protein not only inhibited the macrophage activation, but also skewed M1/M2 balance toward an anti-inflammatory profile, especially enhanced the secretion of IL-10. The activation of TIGIT/PVR pathway in macrophages correlated with increased nuclear translocation of c-Maf, which promotes IL-10 transcription. Treatment with fibroblasts stably secreting TIGIT-Fc fusion protein significantly reversed the lethal and sublethal endotoxic shock, which facilitated peritoneal macrophages to switch towards anti-inflammatory M2 cytokine profiles. These findings highlight a novel role of the TIGIT/PVR pathway in macrophage M2 polarization and suggest that TIGIT may have the potential to optimize the treatment of macrophage-involved inflammatory diseases.
authors: Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China.
authors: Xi
authors: X
authors: Chen
authors: Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China.
authors: Pu-Han
authors: PH
authors: Lu
authors: Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China.
authors: Lei
authors: L
authors: Liu
authors: Department of Cardiothoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China.
authors: Ze-Min
authors: ZM
authors: Fang
authors: Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China.
authors: Wu
authors: W
authors: Duan
authors: Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China.
authors: Zhe-Long
authors: ZL
authors: Liu
authors: Center for Biomedical Research, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China.
authors: Cong-Yi
authors: CY
authors: Wang
authors: Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China.
authors: Ping
authors: P
authors: Zhou
authors: Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China.
authors: Xue-Feng
authors: XF
authors: Yu
authors: Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China. Electronic address: wthe@tjh.tjmu.edu.cn.
authors: Wen-Tao
authors: WT
authors: He
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000401:mortality / Q000473:pathology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D041681:NIH 3T3 Cells; D010641:Phenotype; D051257:Proto-Oncogene Proteins c-maf / Q000235:genetics / Q000276:immunology; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology*; D011991:Receptors, Virus / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D015398:Signal Transduction; D016019:Survival Analysis
chemical_list: C556062:IL10 protein, mouse; D007141:Immunoglobulin Fc Fragments; D008070:Lipopolysaccharides; C495608:Maf protein, mouse; D051257:Proto-Oncogene Proteins c-maf; D011971:Receptors, Immunologic; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; C556305:T cell Ig and ITIM domain protein, mouse; C066100:poliovirus receptor; D016753:Interleukin-10
keywords: LPS; Macrophage; PVR; Polarization; TIGIT