Abstract
T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) is a negative regulator of interferon (IFN)-γ-secreting CD4(+) Th1 cells and plays a key role in autoimmune diseases. Here, we report that galectin-9 expression was increased in hepatic CD4(+)CD25(+) T cells in a mouse model of concanavalin A (Con A)-induced hepatitis. Moreover, Tim-3 showed increased levels in CD4(+)CD25(+) Foxp3(+) regulatory T cells (Tregs). Further analyses showed that blocking the Tim-3/galectin-9 pathway resulted in the suppression of Tregs in vitro, thereby significantly increasing interferon (IFN)-γ production from hepatic Teffs. Moreover, blockade of Tim-3 in vivo with an anti-Tim-3 antibody exacerbated the acute hepatitis, possibly by increased IFN-γ production. Furthermore, we found that in vitro activation of CD4(+)CD25(-) T cells with the T cell receptor (TCR) plus interleukin 2 (IL-2) up-regulated Tim-3 expression. And the induced Tim-3 interacted with galectin-9 to induce CD4(+) T cell apoptosis which could be partly reversed by blocking Tim-3 signaling. Our results suggested that the Tim-3/galectin-9 pathway plays a critical role in the homeostasis of hepatic Tregs through the elimination induction in Teffs and the inhibition ...Continue Reading
References
Jul 1, 1992·The Journal of Clinical Investigation·G TiegsA Wendel
Jun 27, 1998·The Journal of Biological Chemistry·R MatsumotoM Hirashima
Feb 2, 2002·Nature·Laurent MonneyVijay K Kuchroo
May 31, 2002·International Archives of Allergy and Immunology·Naoki SaitaMitsuomi Hirashima
Jul 13, 2002·International Journal of Cancer. Journal International Du Cancer·Toshiro KageshitaMitsuomi Hirashima
Jan 4, 2003·Nature Reviews. Immunology·Ian Nicholas Crispe
Jan 8, 2003·The Journal of Experimental Medicine·Kevin J MaloyFiona Powrie
Oct 14, 2003·Nature Immunology·Catherine A SabatosVijay K Kuchroo
Aug 20, 2005·Trends in Immunology·David G BowenPatrick Bertolino
Nov 16, 2005·Nature Immunology·Chen ZhuVijay K Kuchroo
Jul 1, 2006·Journal of Leukocyte Biology·Akiko Toda, Ciriaco A Piccirillo
Oct 3, 2006·Current Opinion in Immunology·Ana C Anderson, David E Anderson
Jan 30, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Annette ErhardtGisa Tiegs
May 25, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Zhongjun DongZhigang Tian
Feb 20, 2008·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Masako SekiMitsuomi Hirashima
Jan 3, 2009·Immunity·Thomas KaufmannAndreas Strasser
Apr 14, 2009·Immunobiology·Feng WangZhonghua Klaus Chen
Mar 31, 2011·Scandinavian Journal of Rheumatology·J LeeH-S Cha
Mar 1, 2012·PloS One·Xin GaoBinfeng Lu
Apr 17, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Hang LiWeiping Zou
Jun 20, 2012·Gastroenterology·Patrick T F KennedyAntonio Bertoletti
Nov 3, 2012·PloS One·Kun LvQifeng Suo
Citations
Jun 7, 2014·DNA and Cell Biology·Mingfei WangQunfeng Guo
Sep 10, 2015·FEBS Letters·Ada G BlidnerGabriel A Rabinovich
Nov 26, 2015·Gastroenterology Clinics of North America·David E Kaplan
Jun 1, 2016·Frontiers in Immunology·Jacobo López-AbenteMarjorie Pion
Mar 24, 2018·Clinical and Experimental Immunology·Y GuoY Guo
Sep 5, 2019·The Journal of Clinical Investigation·Yufeng LiuJie Zhou
Sep 6, 2019·Scandinavian Journal of Immunology·Lizhen ZhaoBei Zhang
Nov 5, 2019·Nature Reviews. Immunology·Yochai WolfVijay K Kuchroo
Feb 24, 2016·World Journal of Gastroenterology : WJG·Yuan LiuChun-Hong Ma
Mar 5, 2016·PloS One·Yan ZhuangMin Wu
Oct 20, 2015·World Journal of Gastroenterology : WJG·Li-Sha ChengWei Jiang
Dec 22, 2020·PloS One·Kiyoshi MigitaHiroshi Yatsuhashi
Feb 10, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Zhifang ChenJianbing Ding
Oct 30, 2020·Frontiers in Immunology·Han WangDean Tian
Feb 23, 2020·Toxicology·Xiaohua HaoHongshan Wei
May 14, 2021·Molecular Immunology·Jiamin XuYingmei Tang
Jul 6, 2021·International Immunopharmacology·Lizhen ZhaoShengwei Xu
Feb 13, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Tingting WangLi Yang
Nov 16, 2021·Frontiers in Immunology·Adel Abo MansourAsif Jilani Iqbal