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- Title
HCV-infected hepatocytes drive CD4<sup>+</sup> CD25<sup>+</sup> Foxp3<sup>+</sup> regulatory T-cell development through the Tim-3/ Gal-9 pathway.
- Authors
Ji, Xiao J.; Ma, Cheng J.; Wang, Jia M.; Wu, Xiao Y.; Niki, Toshiro; Hirashima, Mitsumi; Moorman, Jonathan P.; Yao, Zhi Q.
- Abstract
HCV is remarkable at disrupting human immunity to establish chronic infection. The accumulation of Treg cells at the site of infection and upregulation of inhibitory signaling pathways (such as T-cell Ig and mucin domain protein-3 ( Tim-3) and galectin-9 ( Gal-9)) play pivotal roles in suppressing antiviral effector T ( Teff) cells that are essential for viral clearance. While Tim-3/ Gal-9 interactions have been shown to negatively regulate Teff cells, their role in regulating Treg cells is poorly understood. To explore how Tim-3/ Gal-9 interactions regulate HCV-mediated Treg-cell development, here we provide pilot data showing that HCV-infected human hepatocytes express higher levels of Gal-9 and TGF-β, and upregulate Tim-3 expression and regulatory cytokines TGF-β/ IL-10 in co-cultured human CD4+ T cells, driving conventional CD4+ T cells into CD25+ Foxp3+ Treg cells. Additionally, recombinant Gal-9 protein can transform TCR-activated CD4+ T cells into Foxp3+ Treg cells in a dose-dependent manner. Importantly, blocking Tim-3/ Gal-9 ligations abrogates HCV-mediated Treg-cell induction by HCV-infected hepatocytes, suggesting that Tim-3/ Gal-9 interactions may regulate human Foxp3+ Treg-cell development and function during HCV infection.
- Publication
European Journal of Immunology, 2013, Vol 43, Issue 2, p458
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.201242768