dc.contributor.author | Mengshol, John A. | |
dc.contributor.author | Golden-Mason, Lucy | |
dc.contributor.author | Arikawa, Tomohiro | |
dc.contributor.author | Smith, Maxwell | |
dc.contributor.author | Niki, Toshiro | |
dc.contributor.author | McWilliams, Ryan | |
dc.contributor.author | Randall, Jessica A. | |
dc.contributor.author | McMahan, Rachel | |
dc.contributor.author | Zimmerman, Michael A. | |
dc.contributor.author | Dobrinskikh, Evgenia | |
dc.contributor.author | Busson, Pierre | |
dc.contributor.author | Polyak, Stephen J. | |
dc.contributor.author | Hirashima, Mitsuomi | |
dc.contributor.author | Rosen, Hugo R. | |
dc.contributor.author | Rangachari, Manu V. | |
dc.date.accessioned | 2011-04-28T06:12:38Z | |
dc.date.issued | 2010 | |
dc.identifier.citation | Mengshol, John A., Lucy Golden-Mason, Tomohiro Arikawa, Maxwell Smith, Toshiro Niki, Ryan McWilliams, Jessica A. Randall, et al. 2010. A crucial role for Kupffer cell-derived galectin-9 in regulation of T cell immunity in Hepatitis C infection. PLoS ONE 5(3): e9504. | en_US |
dc.identifier.issn | 1932-6203 | en_US |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:4878940 | |
dc.description.abstract | Approximately 200 million people throughout the world are infected with hepatitis C virus (HCV). One of the most striking features of HCV infection is its high propensity to establish persistence (∼70–80%) and progressive liver injury. Galectins are evolutionarily conserved glycan-binding proteins with diverse roles in innate and adaptive immune responses. Here, we demonstrate that galectin-9, the natural ligand for the T cell immunoglobulin domain and mucin domain protein 3 (Tim-3), circulates at very high levels in the serum and its hepatic expression (particularly on Kupffer cells) is significantly increased in patients with chronic HCV as compared to normal controls. Galectin-9 production from monocytes and macrophages is induced by IFN-γ, which has been shown to be elevated in chronic HCV infection. In turn, galectin-9 induces pro-inflammatory cytokines in liver-derived and peripheral mononuclear cells; galectin-9 also induces anti-inflammatory cytokines from peripheral but not hepatic mononuclear cells. Galectin-9 results in expansion of CD4+CD25+FoxP3+CD127low regulatory T cells, contraction of CD4+ effector T cells, and apoptosis of HCV-specific CTLs. In conclusion, galectin-9 production by Kupffer cells links the innate and adaptive immune response, providing a potential novel immunotherapeutic target in this common viral infection. | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | Public Library of Science | en_US |
dc.relation.isversionof | doi:10.1371/journal.pone.0009504 | en_US |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831996/pdf/ | en_US |
dash.license | LAA | |
dc.subject | immunology | en_US |
dc.subject | immune response | en_US |
dc.subject | virology | en_US |
dc.subject | immune evasion | en_US |
dc.subject | gastroenterology and hepatology | en_US |
dc.subject | hepatology | en_US |
dc.subject | infectious diseases | en_US |
dc.subject | viral infections | en_US |
dc.title | A Crucial Role for Kupffer Cell-Derived Galectin-9 in Regulation of T Cell Immunity in Hepatitis C Infection | en_US |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en_US |
dc.relation.journal | PLoS ONE | en_US |
dash.depositing.author | Rangachari, Manu V. | |
dc.date.available | 2011-04-28T06:12:38Z | |
dash.affiliation.other | HMS^Neurology-Brigham and Women's Hospital | en_US |
dc.identifier.doi | 10.1371/journal.pone.0009504 | * |
dash.authorsordered | false | |
dash.contributor.affiliated | Rangachari, Manu V. | |