标题:PGRN protects against colitis progression in mice in an IL-10 and TNFR2 dependent manner
作者:Wei, Fanhua; Zhang, Yuying; Jian, Jinlong; Mundra, Jyoti Joshi; Tian, Qingyun; Lin, Jiqiang; Lafaille, Juan Jose; Tang, Wei; Zhao, Wei 更多
作者机构:[Wei, Fanhua; Zhang, Yuying; Jian, Jinlong; Mundra, Jyoti Joshi; Tian, Qingyun; Liu, Chuan-Ju] NYU, Med Ctr, Dept Orthopaed Surg, New York, NY 10003 U 更多
通讯作者:Liu, CJ
通讯作者地址:[Liu, CJ]NYU, Med Ctr, Dept Orthopaed Surg, New York, NY 10003 USA.
来源:SCIENTIFIC REPORTS
出版年:2014
卷:4
DOI:10.1038/srep07023
摘要:This study was aimed to determine the role and regulation of progranulin (PGRN) in the pathogenesis of inflammatory bowel diseases (IBD). Dextran sulfate sodium (DSS)-, picrylsulfonic acid (TNBS)-induced, bone marrow chimera and CD4+CD45Rb(hi) T cell transfer colitis model were established and analyzed in wild-type and several genetically-modified mice, including PGRN, IL-10 and TNFR2 deficient mice. Elevated levels of PGRN were found in colitis samples from human IBD patients and mouse colitis models in comparison to the corresponding controls. PGRN-deficient mice became highly susceptible to DSS- and TNBS-induced colitis, whereas recombinant PGRN ameliorated the pathology and reduced the histological score in both DSS and TNBS colitis models. In addition, hematopoietic-derived PGRN was critical for protection against DSS-induced colitis, and lack of PGRN signaling in CD4+ T cells also exacerbated experimental colitis. PGRN-mediated protective effect in colitis was compromised in the absence of IL-10 signaling. In addition, PGRN's effect was also largely lost in the TNFR2-deficient colitis model. Collectively, these findings not only provide the new insight into PGRN's anti-inflammatory action in vivo, but may also present PGRN and its derivatives as novel biological agent for treating IBD.
收录类别:SCIE
WOS核心被引频次:19
资源类型:期刊论文
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