AKI后，TECs在G2/M期阻滞是触发“适应不良性修复”的关键之一。我们研究表明，在AKI修复期，DCs细胞内NFκB非经典途径可促进IDO的表达、Mφ浸润和Tregs增殖，有利于肾脏修复。相关研究表明，IDO上调可抑制皮肤组织细胞G2/M期阻滞，促进修复；IDO缺乏则引起细胞G2/M期阻滞，促进纤维化因子产生和疤痕的形成。由于表达IDO的IDO+DCs与Tregs之间相互作用影响着IDO的产生，而IDO在DCs与Tregs之间充当桥梁作用。因此，我们提出科学假说：适应不良性修复是由于肾脏中IDO+DCs与Tregs相互作用异常、IDO生成不足、导致TECs在G2/M期阻滞、上调促纤维化分子表达而引起的。本课题将使用KO小鼠模型，采用细胞共培养，研究IDO+DCs与Tregs间相互作用对TECs在G2/M期阻滞、以及促纤维化因子的影响，阐明肾脏纤维化的机制。

The G2/M arrest of tubular epeithlial cells is a key point of “maladaptive repair”. Our previous studies revealed that the expression of indoleamine 2,3-dioxygenase (IDO) in DCs is consistence with the increase of Mφ infiltration and T cells proliferation，which benefits to tissue restoration after renal IRI. The upregulation of IDO could inhibit the G2/M arrest of skin tissue and induce reapir. An important feature of the maladaptive repair process after severe injury is the development of cell cycle arrest in G2/M, which leads to DNA repair response by releasing profibrotic factors. Furthermore, studies show that IDO acts as a bridge between dendritic cells (DCs) and regulatory T cells (Tregs ). We hypothesized that the insufficient production of IDO would result in tubular epithelial cell cycle arrest at G2/M and promote subsequent downstream signaling of profibrotic factors, which lead to tubular atrophy and tubularintersitum fibrosis, eventually. Because of IDO acts as a bridge between DCs and regulatory Tregs, the of loss IDO production and Tregs proliferation might attribute to the abnormal cross-talk between IDO+DCs and Tregs. .To test this hypothesis, monocytes Ly6C+, naïve T cells and tubular epithelial cells will be isolated and co-cultured in vitro and IDO+DCs adoptive transfer will be used in vivo in this study to elucidate the molecular mechanism of IDO and cross-talk between IDO+DCs and Tregs in kidney maladaptive repair after AKI, and further to provide a novel clue for preventing AKI-CKD transition