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

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Title: A Crucial Role for Kupffer Cell-Derived Galectin-9 in Regulation of T Cell Immunity in Hepatitis C Infection
Author: Mengshol, John A.; Golden-Mason, Lucy; Arikawa, Tomohiro; Smith, Maxwell; Niki, Toshiro; McWilliams, Ryan; Randall, Jessica A.; McMahan, Rachel; Zimmerman, Michael A.; Dobrinskikh, Evgenia; Busson, Pierre; Polyak, Stephen J.; Hirashima, Mitsuomi; Rosen, Hugo R.; Rangachari, Manu V.

Note: Order does not necessarily reflect citation order of authors.

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.
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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.
Published Version: doi:10.1371/journal.pone.0009504
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831996/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:4878940

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