CHI3L1 protects TAA-induced liver injury via regulating STAT3-mediated T cell differentiation
详细信息 查看官网全文
- 英文论文题名：CHI3L1 protects TAA-induced liver injury via regulating STAT3-mediated T cell differentiation
- 论文作者：Jian Gu ; Yunjie Lu ; Hao Lu ; Xuhao Ni ; Ling Lu
- 英文论文作者：Jian Gu ; Yunjie Lu ; Hao Lu ; Xuhao Ni ; Ling Lu ; Nanjing Medical University
- 年：2016
- 作者机构：Nanjing Medical University;
- 英文论文关键词：Liver injury ; CHI3L1 ; IFN-r ; Foxp3
- 会议召开时间：2016-11-04
- 会议录名称：第十一届全国免疫学学术大会摘要汇编
- 英文会议录名称：Abstracts of 2016 CSI Congress on Immunology
- 语种：英文
- 分类号：R575
- 学会代码：IGMD
- 会议名称：第十一届全国免疫学学术大会
- 会议地点：中国安徽合肥
- 主办单位：中国免疫学会
- 学会名称：中国免疫学会
- 页数：1
- 文件大小：231k
- 原文格式：D
- 会议级别：全国
摘要
Background and aims: Chitinase 3–like 1(CHI3L1) is a prototypic chitinase-like protein that has been retained over species and evolutionary time. The role of CHI3L1 in liver injury and liver failure has not been defined. This study was designed to dissect the functional role and potential mechanism of CHI3L1 in TAA-induced liver injury. Methods: Murine liver injury model was established by injection of TAA. CHI3L1 as well as CHI3L1-ko mice were used to determine the role of CHI3L1 in liver injury. To investigate the mechanism of CHI3L1 in protecting liver injury, the level of STAT3 and IFN-r were measured. Results: The CHI3L1 levels were decreased in patients after liver injury. High levels of CHI3L1 are associated with the improvement of liver function followed by medical treatment. To determine the role and mechanism of CHI3L1 in liver failure, mouse TAA-induced injury model was used. Injection of a recombinant CHI3L1(r CHI3L1) reduced the liver damage and improved liver function. However, knockout of CHI3LI(CHI3LI KO) resulted in exacerbating liver injury, as evidenced by increasing serum ALT and liver damage histologically. Unlike in controls, r CHI3L1 treatment decreased the expression of T-bet, IFN-r, and Th17 but increased Foxp3 regulatory T cells(Foxp3+Tregs). CHI3L1 treatment decreased the phosphorylation of STAT3, while CHI3L1 knockout increased STAT3 phosphorylation. Moreover, administration of recombinant m IFN-r or STAT3 inhibitor increased TAA-induced liver injury, which accompanied by increased Th17 and reduced Foxp3 expression in CHI3LI-deficient mice. Conclusion: This study demonstrates that CHI3 LI protects livers against TAA-induced liver injury. CHI3LI-mediated hepato-protection by inhibiting Th17 and promoting Foxp3+Tregs in a Stat3-dependent manner. Our findings established the regulatory role of CHI3L1 in liver injury, and provides the novel therapeutic targets in in liver injury and liver failure.
Background and aims: Chitinase 3–like 1(CHI3L1) is a prototypic chitinase-like protein that has been retained over species and evolutionary time. The role of CHI3L1 in liver injury and liver failure has not been defined. This study was designed to dissect the functional role and potential mechanism of CHI3L1 in TAA-induced liver injury. Methods: Murine liver injury model was established by injection of TAA. CHI3L1 as well as CHI3L1-ko mice were used to determine the role of CHI3L1 in liver injury. To investigate the mechanism of CHI3L1 in protecting liver injury, the level of STAT3 and IFN-r were measured. Results: The CHI3L1 levels were decreased in patients after liver injury. High levels of CHI3L1 are associated with the improvement of liver function followed by medical treatment. To determine the role and mechanism of CHI3L1 in liver failure, mouse TAA-induced injury model was used. Injection of a recombinant CHI3L1(r CHI3L1) reduced the liver damage and improved liver function. However, knockout of CHI3LI(CHI3LI KO) resulted in exacerbating liver injury, as evidenced by increasing serum ALT and liver damage histologically. Unlike in controls, r CHI3L1 treatment decreased the expression of T-bet, IFN-r, and Th17 but increased Foxp3 regulatory T cells(Foxp3+Tregs). CHI3L1 treatment decreased the phosphorylation of STAT3, while CHI3L1 knockout increased STAT3 phosphorylation. Moreover, administration of recombinant m IFN-r or STAT3 inhibitor increased TAA-induced liver injury, which accompanied by increased Th17 and reduced Foxp3 expression in CHI3LI-deficient mice. Conclusion: This study demonstrates that CHI3 LI protects livers against TAA-induced liver injury. CHI3LI-mediated hepato-protection by inhibiting Th17 and promoting Foxp3+Tregs in a Stat3-dependent manner. Our findings established the regulatory role of CHI3L1 in liver injury, and provides the novel therapeutic targets in in liver injury and liver failure.
Background and aims: Chitinase 3–like 1(CHI3L1) is a prototypic chitinase-like protein that has been retained over species and evolutionary time. The role of CHI3L1 in liver injury and liver failure has not been defined. This study was designed to dissect the functional role and potential mechanism of CHI3L1 in TAA-induced liver injury. Methods: Murine liver injury model was established by injection of TAA. CHI3L1 as well as CHI3L1-ko mice were used to determine the role of CHI3L1 in liver injury. To investigate the mechanism of CHI3L1 in protecting liver injury, the level of STAT3 and IFN-r were measured. Results: The CHI3L1 levels were decreased in patients after liver injury. High levels of CHI3L1 are associated with the improvement of liver function followed by medical treatment. To determine the role and mechanism of CHI3L1 in liver failure, mouse TAA-induced injury model was used. Injection of a recombinant CHI3L1(r CHI3L1) reduced the liver damage and improved liver function. However, knockout of CHI3LI(CHI3LI KO) resulted in exacerbating liver injury, as evidenced by increasing serum ALT and liver damage histologically. Unlike in controls, r CHI3L1 treatment decreased the expression of T-bet, IFN-r, and Th17 but increased Foxp3 regulatory T cells(Foxp3+Tregs). CHI3L1 treatment decreased the phosphorylation of STAT3, while CHI3L1 knockout increased STAT3 phosphorylation. Moreover, administration of recombinant m IFN-r or STAT3 inhibitor increased TAA-induced liver injury, which accompanied by increased Th17 and reduced Foxp3 expression in CHI3LI-deficient mice. Conclusion: This study demonstrates that CHI3 LI protects livers against TAA-induced liver injury. CHI3LI-mediated hepato-protection by inhibiting Th17 and promoting Foxp3+Tregs in a Stat3-dependent manner. Our findings established the regulatory role of CHI3L1 in liver injury, and provides the novel therapeutic targets in in liver injury and liver failure.
引文