Copyright
©The Author(s) 2015.
World J Gastroenterol. Oct 14, 2015; 21(38): 10721-10731
Published online Oct 14, 2015. doi: 10.3748/wjg.v21.i38.10721
Published online Oct 14, 2015. doi: 10.3748/wjg.v21.i38.10721
Table 1 Role of Treg and Th17 cell-related interleukins in chronic hepatitis
Treg and Th17-related interleukins | Cellular sources | Roles in CD4+ T cell differentiation and function | Roles in liver inflammation and fibrosis | Ref. |
IL-17 | Th17, neutrophils, NKT cells, macrophages, γδT cells | Characteristic cytokine of Th17 cells: pro-inflammatory | Pro-inflammatory | [6-8,10,31] |
Pro-fibrotic | ||||
IL-21 | Th17, Tfh, NKT cells | Promotes differentiation of Th17 cells; | Promotes HBV-related liver injury and fibrogenesis | [18,21,28-30] |
Inhibits differentiation of Treg cells | ||||
IL-23 | DCs, macrophages | Promotes Th17 cell proliferation and stabilizes effector Th17 cells | Promotes HBV-related liver injury | [22,80] |
IL-22 | Th17, Th22, activated NK and NKT cells | Characteristic cytokine of Th22 cells: pro-inflammatory | Hepatoprotective? Pro-inflammatory? Pro-fibrotic? Anti-fibrotic? | [23,24,26,27] |
IL-10 | Treg, hepatocytes, Kupffer cells, LSECs, HSCs, Breg | Inhibits Th1, Th2, Th17 cell differentiation and cytokine production | Anti-inflammatory | [35,38,81] |
Anti-fibrotic | ||||
IL-35 | Treg, Breg | Immunosuppressive | Anti-inflammatory | [30,31,33,34] |
Anti-fibrotic? | ||||
IL-33 | LSECs, activated HSCs | Promotes Th2 differentiation and cytokine production;Increases Treg cells?Activates Tfh cells? | Pro-fibrotic | [86-88,90,91] |
Anti-inflammatory? |
Table 2 Role of surface molecules in chronic hepatitis
Surface molecules | Expression on T cells and CD4+ T cell subsets | General effects | Role in liver inflammation and fibrosis | CD4+ T cell response to blocking | Ref. |
PD-1 | CD8+ T cells | Inhibits T cell activation; | Causes exhaustion of HBV-specific CD8+ and CD4+ T cells | Partially-revived proliferation and function | [96-98,104] |
CD4+ T cells | Maintains tolerance | ||||
TIM-3 | CD8+ T cells | Inhibits T cell activation; Maintains tolerance | Promotes progression of HBV infection | Revived more (blocked with PD-1) | [99,100,102-104] |
CD4+ T cells | |||||
Treg cells | |||||
CTLA-4 | Activated CD4+ T cells | Inhibits CD4+ T cell over-activation; | Promotes persistence of HBV and progression of HBV infection | Unknown | [105,107,109,110] |
Treg cells | Maintains tolerance | ||||
CB2 | CD4+ T cells | Immunoregulatory: pro-inflammatory or anti-inflammatory; Anti-fibrotic | Anti-inflammatory;Anti-fibrotic;Hepatoprotective? | Decreased frequency and function of Th17 cells | [112-114] |
CD8+ T cells | |||||
Th17 cells |
- Citation: Cheng LS, Liu Y, Jiang W. Restoring homeostasis of CD4+ T cells in hepatitis-B-virus-related liver fibrosis. World J Gastroenterol 2015; 21(38): 10721-10731
- URL: https://www.wjgnet.com/1007-9327/full/v21/i38/10721.htm
- DOI: https://dx.doi.org/10.3748/wjg.v21.i38.10721