Author(s): Lizhen Zhao, Mengli Cui, Dan Xu, Qi Han, Bei Zhang
Acute liver injury refers to diseases caused by various factors such as explosive liver dysfunction and inflammatory reaction caused by various causes, and the main mechanism is unclear. In this study, we found that T cell Ig and mucin domain protein 3 (Tim-3) play an important role in CCl4-induced acute liver injury. Using antibodies against the Tim-3 antibody (anti-Tim-3Ab), we studied the Tim-3 signal in an animal model of acute liver injury and found that a large number of inflammatory factors were released. Administration of galectin-9 (Gal-9 is a Tim-3 ligand) reduced the production of IL-1β and IL-6 in spleen lymphocytes. This indicates the importance of the Tim-3 / Gal-9 signaling pathway in maintaining liver homeostasis. This finding is potentially important for the treatment of early liver damage.
- Swann, J.B. and M.J. Smyth, Immune surveillance of tumors. J Clin Invest, 2007. 117(5): p. 1137-46.
- Pentcheva-Hoang, T., E. Corse, and J.P. Allison, Negative regulators of T-cell activation: potential targets for therapeutic intervention in cancer, autoimmune disease, and persistent infections. Immunol Rev, 2009. 229(1): p. 67-87.
- Monney, L., et al., Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease. Nature, 2002. 415(6871): p. 536-41.
- Chiba, S., et al., Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1. Nat Immunol, 2012. 13(9): p. 832-42.
- Anderson, A.C., et al., Promotion of tissue inflammation by the immune receptor Tim-3 expressed on innate immune cells. Science, 2007. 318(5853): p. 1141-3.
- Nagahara, K., et al., Galectin-9 increases Tim-3+ dendritic cells and CD8+ T cells and enhances antitumor immunity via galectin-9-Tim-3 interactions. J Immunol, 2008. 181(11): p. 7660-9.
- Ndhlovu, L.C., et al., Tim-3 marks human natural killer cell maturation and suppresses cell-mediated cytotoxicity. Blood, 2012. 119(16): p. 3734-43.
- Ju, Y., et al., T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) mediates natural killer cell suppression in chronic hepatitis B. J Hepatol, 2010. 52(3): p. 322-9.
- Golden-Mason, L., et al., Negative immune regulator Tim-3 is overexpressed on T cells in hepatitis C virus infection and its blockade rescues dysfunctional CD4+ and CD8+ T cells. J Virol, 2009. 83(18): p. 9122-30.
- Jin, H.T., et al., Cooperation of Tim-3 and PD-1 in CD8 T-cell exhaustion during chronic viral infection. Proc Natl Acad Sci U S A, 2010. 107(33): p. 14733-8.
- Yan, W., et al., Tim-3 fosters HCC development by enhancing TGF-beta-mediated alternative activation of macrophages. Gut, 2015. 64(10): p. 1593-604.
- Rong, Y.H., et al., Tim-3 expression on peripheral monocytes and CD3+CD16/CD56+natural killer-like T cells in patients with chronic hepatitis B. Tissue Antigens, 2014. 83(2): p. 76-81.
- Wang, J.M., et al., Differential regulation of interleukin-12 (IL-12)/IL-23 by Tim-3 drives T(H)17 cell development during hepatitis C virus infection. J Virol, 2013. 87(8): p. 4372-83.
- Ngiow, S.F., M.W. Teng, and M.J. Smyth, Prospects for TIM3-Targeted Antitumor Immunotherapy. Cancer Res, 2011. 71(21): p. 6567-71.
- da Silva, I.P., et al., Reversal of NK-cell exhaustion in advanced melanoma by Tim-3 blockade. Cancer Immunol Res, 2014. 2(5): p. 410-22.
- Wiener, Z., et al., TIM-3 is expressed in melanoma cells and is upregulated in TGF-beta stimulated mast cells. J Invest Dermatol, 2007. 127(4): p. 906-14.
- Anderson, A.C., Tim-3, a negative regulator of anti-tumor immunity. Curr Opin Immunol, 2012. 24(2): p. 213-6.
- McIntire, J.J., et al., Identification of Tapr (an airway hyperreactivity regulatory locus) and the linked Tim gene family. Nat Immunol, 2001. 2(12): p. 1109-16.
- Meyers, J.H., et al., TIM-4 is the ligand for TIM-1, and the TIM-1-TIM-4 interaction regulates T cell proliferation. Nat Immunol, 2005. 6(5): p. 455-64.
- Zhu, C., et al., The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat Immunol, 2005. 6(12): p. 1245-52.
- Sabatos, C.A., et al., Interaction of Tim-3 and Tim-3 ligand regulates T helper type 1 responses and induction of peripheral tolerance. Nat Immunol, 2003. 4(11): p. 1102-10.
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