Richard Flavell

Publications (2)11.66 Total impact

• Source

  Available from: Patrick S C Leung

  Dataset: Deletion of Interleukin (IL)-12p35 Induces Liver Fibrosis in Dominant-Negative TGFb Receptor Type II Mice

  Masanobu Tsuda, Weici Zhang, Guo-Xiang Yang, Koichi Tsuneyama, Yugo Ando, Kazuhito Kawata, Ogyi Park, Patrick S C Leung, Ross L Coppel, Aftab A Ansari, William M Ridgway, Bin Gao, Zhe-Xiong Lian, Richard Flavell, Xiao-Song He, M Eric Gershwin
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  ABSTRACT: Mice with a dominant-negative transforming growth factor b receptor restricted to T cells (dnTGFbRII mice) develop an inflammatory biliary ductular disease that strongly resembles human primary biliary cirrhosis (PBC). Furthermore, deletion of the gene encoding interleukin (IL)-12p40 resulted in a strain (IL-12p40 2/2 dnTGFbRII) with dramatically reduced autoim-mune cholangitis. To further investigate the role of the IL-12 cytokine family in dnTGFbRII autoimmune biliary disease, we deleted the gene encoding the IL-12p35 subunit from dnTGFbRII mice, resulting in an IL-12p35 2/2 dnTGFbRII strain which is deficient in two members of the IL-12 family, IL-12 and IL-35. In contrast to IL-12p40 2/2 mice, the IL-12p35 2/2 mice developed liver inflammation and bile duct damage with similar severity but delayed onset as the parental dnTGFbRII mice. The p35 2/2 mice also demonstrated a distinct cytokine profile characterized by a shift from a T-helper 1 (Th1) to a Th17 response. Strikingly, liver fibrosis was frequently observed in IL-12p35 2/2 mice. In conclusion, IL-12p35 2/2 dnTGFbRII mice, histologically and immunologically, reflect key features of PBC, providing a useful generic model to understand the immunopathology of human PBC. (HEPATOLOGY 2013;57:806-816)
• Source

  Available from: Guo-Xiang Yang

  Article: Deletion of IL-12p35 induces liver fibrosis in dominant negative transforming growth factor β receptor type II mice.

  Masanobu Tsuda, Weici Zhang, Guo-Xiang Yang, Koichi Tsuneyama, Yugo Ando, Kazuhito Kawata, Ogyi Park, Patrick S C Leung, Ross L Coppel, Aftab A Ansari, William M Ridgway, Bin Gao, Zhe-Xiong Lian, Richard Flavell, Xiao-Song He, M Eric Gershwin
  [show abstract] [hide abstract]
  ABSTRACT: We have previously reported that mice with a dominant negative transforming growth factor β receptor restricted to T cells (dnTGFβRII mice) develop an inflammatory biliary ductular disease that strongly resembles human primary biliary cirrhosis (PBC). Furthermore, deletion of the gene encoding interleukin (IL)-12p40 resulted in a strain (IL-12p40(-/-) dnTGFβRII) with dramatically reduced autoimmune cholangitis. To further investigate the role of the IL-12 cytokine family in dnTGFβRII autoimmune biliary disease, we deleted the gene encoding the IL-12p35 subunit from dnTGFβRII mice, resulting in an IL-12p35(-/-) dnTGFβRII strain which is deficient in two members of the IL-12 family, IL-12 and IL-35. In contrast to IL-12p40(-/-) mice, the IL-12p35(-/-) mice developed liver inflammation and bile duct damage with similar severity but delayed onset as the parental dnTGFβRII mice. The p35(-/-) mice also demonstrated a distinct cytokine profile characterized by a shift from a Th1 to a Th17 response. Strikingly, liver fibrosis was frequently observed in IL-12p35(-/-) mice. In conclusion, IL-12p35(-/-) dnTGFβRII mice, histologically and immunologically, reflect key features of PBC, providing a useful generic model to understand the immunopathology of human PBC. (HEPATOLOGY 2012.).
  Hepatology 05/2012; · 11.66 Impact Factor