Abstract
Regulatory T cells (Tregs), which are characterized by expression of CD4, CD25, and Foxp3, play a crucial role in the control of immune responses to both self and non-self Ags. To date, there are only limited data on their role in physiological and pathological hepatic immune responses. In this study, we examined the role of hepatic Tregs in immune-mediated liver injury by using the murine Con A-induced hepatitis model. Con A treatment was associated with an increased number of Foxp3+ Tregs in liver but not in spleen. Moreover, the expression levels of Foxp3, CTLA-4, glucocorticoid-induced TNF receptor, as well as the frequency of CD103 of Tregs were increased after Con A injection, being significantly higher in liver than in spleen. Depleting CD25+ cells aggravated liver injury, whereas adoptively transferring CD25+ cells or Tregs reduced liver injury in Con A-treated recipients. Con A treatment induced elevated serum levels and hepatic mononuclear mRNA expressions of TGF-β, which were reduced by Tregs depletion. In addition, anti-TGF-β mAbs blocked the suppressive function of Tregs from Con A-treated mice in vitro. Finally, TGF-β receptor II dominant-negative mice, whose T cells express a dominant negative form of TGFβRII and therefore cannot respond to TGF-β, had a higher mortality rate and severer liver injury than normal mice injected with the same dose of Con A. These results indicate that CD4+CD25+ Tregs play an important role in limiting the liver injury in Con A-induced hepatitis via a TGF-β-dependent mechanism.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 7221-7229 |
| Number of pages | 9 |
| Journal | Journal of Immunology |
| Volume | 181 |
| Issue number | 10 |
| State | Published - Nov 15 2008 |
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ASJC Scopus subject areas
- Immunology
- Medicine(all)
Cite this
CD4+CD25+ Foxp3+ regulatory T cells protect against T cell-mediated fulminant hepatitis in a TGF-β-dependent manner in mice. / Wei, Hua Xing; Chuang, Ya Hui; Li, Bofeng; Wei, Haiming; Sun, Rui; Moritoki, Yuki; Gershwin, M. Eric; Lian, Zhe Xiong; Tian, Zhigang.
In: Journal of Immunology, Vol. 181, No. 10, 15.11.2008, p. 7221-7229.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - CD4+CD25+ Foxp3+ regulatory T cells protect against T cell-mediated fulminant hepatitis in a TGF-β-dependent manner in mice
AU - Wei, Hua Xing
AU - Chuang, Ya Hui
AU - Li, Bofeng
AU - Wei, Haiming
AU - Sun, Rui
AU - Moritoki, Yuki
AU - Gershwin, M. Eric
AU - Lian, Zhe Xiong
AU - Tian, Zhigang
PY - 2008/11/15
Y1 - 2008/11/15
N2 - Regulatory T cells (Tregs), which are characterized by expression of CD4, CD25, and Foxp3, play a crucial role in the control of immune responses to both self and non-self Ags. To date, there are only limited data on their role in physiological and pathological hepatic immune responses. In this study, we examined the role of hepatic Tregs in immune-mediated liver injury by using the murine Con A-induced hepatitis model. Con A treatment was associated with an increased number of Foxp3+ Tregs in liver but not in spleen. Moreover, the expression levels of Foxp3, CTLA-4, glucocorticoid-induced TNF receptor, as well as the frequency of CD103 of Tregs were increased after Con A injection, being significantly higher in liver than in spleen. Depleting CD25+ cells aggravated liver injury, whereas adoptively transferring CD25+ cells or Tregs reduced liver injury in Con A-treated recipients. Con A treatment induced elevated serum levels and hepatic mononuclear mRNA expressions of TGF-β, which were reduced by Tregs depletion. In addition, anti-TGF-β mAbs blocked the suppressive function of Tregs from Con A-treated mice in vitro. Finally, TGF-β receptor II dominant-negative mice, whose T cells express a dominant negative form of TGFβRII and therefore cannot respond to TGF-β, had a higher mortality rate and severer liver injury than normal mice injected with the same dose of Con A. These results indicate that CD4+CD25+ Tregs play an important role in limiting the liver injury in Con A-induced hepatitis via a TGF-β-dependent mechanism.
AB - Regulatory T cells (Tregs), which are characterized by expression of CD4, CD25, and Foxp3, play a crucial role in the control of immune responses to both self and non-self Ags. To date, there are only limited data on their role in physiological and pathological hepatic immune responses. In this study, we examined the role of hepatic Tregs in immune-mediated liver injury by using the murine Con A-induced hepatitis model. Con A treatment was associated with an increased number of Foxp3+ Tregs in liver but not in spleen. Moreover, the expression levels of Foxp3, CTLA-4, glucocorticoid-induced TNF receptor, as well as the frequency of CD103 of Tregs were increased after Con A injection, being significantly higher in liver than in spleen. Depleting CD25+ cells aggravated liver injury, whereas adoptively transferring CD25+ cells or Tregs reduced liver injury in Con A-treated recipients. Con A treatment induced elevated serum levels and hepatic mononuclear mRNA expressions of TGF-β, which were reduced by Tregs depletion. In addition, anti-TGF-β mAbs blocked the suppressive function of Tregs from Con A-treated mice in vitro. Finally, TGF-β receptor II dominant-negative mice, whose T cells express a dominant negative form of TGFβRII and therefore cannot respond to TGF-β, had a higher mortality rate and severer liver injury than normal mice injected with the same dose of Con A. These results indicate that CD4+CD25+ Tregs play an important role in limiting the liver injury in Con A-induced hepatitis via a TGF-β-dependent mechanism.
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M3 - Article
VL - 181
SP - 7221
EP - 7229
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 10
ER -