我们发现生长因子PGRN通过与TNFR结合，特异性阻断TNF/TNFR信号通路实现其抗炎作用，这一成果公布于《SCIENCE》上，回答了PGRN发现20余年来的关键问题。细胞内炎症反应信号通路与UPR偶联是引发炎症反应的主要原因，但是PGRN介导的炎症反应与UPR的关系不清楚。前期研究显示CIA小鼠滑膜成纤维细胞中UPR重要分子IRE1α下调PGRN转录和表达；Grn-/-KO小鼠关节滑液IRE1α表达增加，提示IRE1α可能与PGRN信号通路协同调控小鼠炎性关节炎的发生与发展。本研究综合运用IRE1α转基因小鼠、IRE1α-/-KO小鼠、Grn-/-KO小鼠、CIA等不同类型小鼠模型，结合小鼠体外趾骨组织团块及细胞培养方法，检测IRE1α在小鼠炎性关节炎中的作用与功能；明确IRE1α调控小鼠炎性关节炎是否依赖于PGRN；解析IRE1α与PGRN双信号通路共同调控小鼠炎性关节炎的发病机制。

We testified that the growth factor PGRN can interact with TNFR,then prevents TNF/TNFR signal pathway specifically and achieves its anti-inflammation，which has been published on the famous journal "SCIENCE".This achievement explained the key function of PGRN very well after it was founded twenty years.The main reason of trigger inflammation is intracellular inflammation signal pathway coupling with unfolded protein response(UPR),however, the relationship between PGRN-mediated inflammation and UPR remains unknown.Our previous results showed that IRE1α downregulated PGRN transcription and expression in synovial fibroblasts of CIA mice,and IRE1α expression was increased in synovial fluids of Grn-/-KO mice. It was suggested that both IRE1α and PGRN signal pathway might be co-regulated occurrence and development of inflammatory arthritis in mice.In this study,we utilized IRE1αtransgenetic mice,IRE1α-/-KO mice、Grn-/-KO mice and CIA mice model synthetically,mouse metatarsal bones induced culture in vitro,and cell culture. On basis of these methods,we focus on the relationship between IRE1α and inflammatory arthritis in mice,explore the effect and function of IRE1α in inflammatory arthritis in mice,determine whether IRE1α regulation inflammatory arthritis depends on PGRN ,analyse on the interplay between IRE1α and PGRN signaling in mediating the pathogenesis of inflammatory arthritis in mice.