A Crucial Role for Kupffer Cell-Derived Galectin-9 in Regulation of T Cell Immunity in Hepatitis C Infection

A Crucial Role for Kupffer Cell-Derived Galectin-9 in Regulation of T Cell Immunity in Hepatitis C Infection

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A Crucial Role for Kupffer Cell-Derived Galectin-9 in Regulation of T Cell Immunity in Hepatitis C Infection

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