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
通讯作者地址：[Liu, CJ]NYU, Med Ctr, Dept Orthopaed Surg, New York, NY 10003 USA.
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.