Cutting edge: a key pathogenic role of IL-27 in T cell- mediated hepatitis.
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Cutting edge: a key pathogenic role of IL-27 in T cell- mediated hepatitis. / Siebler, Juergen; Wirtz, Stefan; Frenzel, Christian; Schuchmann, Marcus; Lohse, Ansgar W.; Galle, Peter R; Neurath, Markus F.
In: J IMMUNOL, Vol. 180, No. 1, 1, 2008, p. 30-33.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Cutting edge: a key pathogenic role of IL-27 in T cell- mediated hepatitis.
AU - Siebler, Juergen
AU - Wirtz, Stefan
AU - Frenzel, Christian
AU - Schuchmann, Marcus
AU - Lohse, Ansgar W.
AU - Galle, Peter R
AU - Neurath, Markus F
PY - 2008
Y1 - 2008
N2 - The signals driving T cell activation in T cell-mediated fulminant hepatitis are not fully understood. In this study, we identify the cytokine IL-27p28/EBI3 as a major pathogenic factor in the ConA model of T cell-mediated hepatitis. We found an up-regulation of hepatic EBI3 and p28 expression and augmented levels of IL-27 in wild-type mice after ConA administration, suggesting a potential pathogenic role of this cytokine in ConA hepatitis. Consistently, IL-27 EBI3-deficient mice were almost completely protected from ConA-induced liver damage. Such protection was associated with reduced levels of IFN-gamma and its signaling proteins pSTAT-1 and T-bet. Finally, in vivo blockade of IL-27 function using a soluble IL-27 receptor fusion protein led to reduced pSTAT1 levels and suppression of liver injury. Taken together, these data demonstrate a key pathogenic role of IL-27 in T cell-mediated liver injury. Furthermore, in vivo blockade of IL-27 emerges as a novel potential therapy for T cell-mediated hepatitis.
AB - The signals driving T cell activation in T cell-mediated fulminant hepatitis are not fully understood. In this study, we identify the cytokine IL-27p28/EBI3 as a major pathogenic factor in the ConA model of T cell-mediated hepatitis. We found an up-regulation of hepatic EBI3 and p28 expression and augmented levels of IL-27 in wild-type mice after ConA administration, suggesting a potential pathogenic role of this cytokine in ConA hepatitis. Consistently, IL-27 EBI3-deficient mice were almost completely protected from ConA-induced liver damage. Such protection was associated with reduced levels of IFN-gamma and its signaling proteins pSTAT-1 and T-bet. Finally, in vivo blockade of IL-27 function using a soluble IL-27 receptor fusion protein led to reduced pSTAT1 levels and suppression of liver injury. Taken together, these data demonstrate a key pathogenic role of IL-27 in T cell-mediated liver injury. Furthermore, in vivo blockade of IL-27 emerges as a novel potential therapy for T cell-mediated hepatitis.
M3 - SCORING: Zeitschriftenaufsatz
VL - 180
SP - 30
EP - 33
JO - J IMMUNOL
JF - J IMMUNOL
SN - 0022-1767
IS - 1
M1 - 1
ER -
