We have read with interest the article published by Rowan et al. in the October 1, 2008 issue of The Journal of Immunology (1). The authors reported for the first time that Ag-specific Th17 cells were induced in patients infected by the hepatitis C virus (HCV). They also indicated that TGF- β and IL-10, which are induced by the viral nonstructural protein 4 (NS4), suppressed Th1 and Th17 responses in HCV-infected patients. Previously, several groups recognized that a combination of IL-6 and TGF-β was necessary for the differentiation of naive T cells into Th17 cells (2, 3, 4). It is very interesting that in HCV-infected patients TGF-β is a potent regulatory cytokine with inhibitory effects on the Th17 response.
We would like to draw attention to other studies that have identified two additional cytokines involved in the induction of Th17 response: IL-23, an essential factor for maintaining the differentiated Th17 cells through its phenotype stabilization (5, 6, 7), and IL-21, which plays a role in amplification of the Th17 response (8, 9).
The Rowan group’s work indicates the potential of further research into the influence of viral NS4 in HCV-infected patients on IL-6, IL-21, and IL-23 expression. One such study might investigate whether suppression of Th17 response in this patient population may be associated with influencing viral NS4 on IL-6, IL-21, and IL-23 levels in addition to its demonstrated role in suppressing the influence of TGF-β and IL-10 on Th17 response.
