| First Author | Zhao N | Year | 2011 |
| Journal | J Immunol | Volume | 187 |
| Issue | 10 | Pages | 5007-14 |
| PubMed ID | 21987663 | Mgi Jnum | J:179637 |
| Mgi Id | MGI:5302785 | Doi | 10.4049/jimmunol.1101315 |
| Citation | Zhao N, et al. (2011) Vgamma4 gammadelta T cell-derived IL-17A negatively regulates NKT cell function in Con A-induced fulminant hepatitis. J Immunol 187(10):5007-14 |
| abstractText | Con A-induced fulminant hepatitis is a well-known animal model for acute liver failure. However, the role of gammadelta T cells in this model is undefined. In this report, using TCR delta(-/-) mice, we demonstrated a protective role of gammadelta T cells in Con A-induced hepatitis model. TCR delta(-/-) mice showed significantly decreased levels of IL-17A and IL-17F in the Con A-treated liver tissue, and reconstitution of TCR delta(-/-) mice with wild-type (Wt), but not IL-17A(-/-), gammadelta T cells significantly reduced hepatitis, strongly suggesting a critical role of IL-17A in mediating the protective effect of gammadelta T cells. Interestingly, only Vgamma4, but not Vgamma1, gammadelta T cells exerted such a protective effect. Furthermore, depletion of NKT cells in TCR delta(-/-) mice completely abolished hepatitis, and NKT cells from Con A-challenged liver tissues of TCR delta(-/-) mice expressed significantly higher amounts of proinflammatory cytokine IFN-gamma than those from Wt mice, indicating that gammadelta T cells protected hepatitis through targeting NKT cells. Finally, abnormal capacity of IFN-gamma production by NKT cells of TCR delta(-/-) mice could only be downregulated by transferring Wt, but not IL-17(-/-), Vgamma4 gammadelta T cells, confirming an essential role of Vgamma4-derived IL-17A in regulating the function of NKT cells. In summary, our report thus demonstrated a novel function of Vgamma4 gammadelta T cells in mediating a protective effect against Con A-induced fulminant hepatitis through negatively regulating function of NKT cells in an IL-17A-dependent manner, and transferring Vgamma4 gammadelta T cells may provide a novel therapeutic approach for this devastating liver disease. |
