自身免疫性肝炎（AIH）是一种T细胞介导的自身免疫性肝病，可导致肝损伤，且长期预后不良。间充质基质细胞（MSC）具有免疫抑制作用，可以治疗 AIH。 CD4 T 细胞表达独特的抑制性 Fcγ 受体 (FcγRIIB)，它是免疫抑制因子可溶性纤维蛋白原样蛋白 2 (sFgl2) 的唯一受体。本研究旨在探讨sFgl2基因修饰的MSCs（sFgl2-MSCs）对AIH的治疗作用。MSCs从小鼠腹股沟脂肪中获得，并与从小鼠脾脏中分选的CD4 T细胞共培养。通过流式细胞术测定 CD4 T 细胞上的 FcγRIIB 表达。通过酶联免疫吸附测定测定用携带 Fgl2 基因和绿色荧光蛋白编码序列的慢病毒载体转染的 MSC 中 sFgl2 的表达。流式细胞术测定Th1细胞、Th17细胞和调节性T细胞（Tregs）的百分比，Western blotting检测细胞与MSC共培养72 h后p-SHP2和p-SMAD2/3的水平。通过体内成像定位MSC后，Con A诱导的实验性AIH小鼠被随机分为4组并进行不同的治疗。 24小时后，检查肝功能和细胞因子水平的组织病理学评分，并通过流式细胞术测定脾脏和肝脏中CD4 T细胞、CD8 T细胞、Treg Th17细胞和Th1细胞的比例。此外，使用免疫组织化学染色检测 T-bet、Foxp3 和 RORγ 阳性细胞的肝脏浸润情况。与 MSC 共培养后，CD4 T 细胞上的 FcγRIIB 表达上调。与sFgl2-MSCs共培养后，CD4 T细胞中Treg细胞比例增加，Th17和Th1细胞比例下降，p-SHP2和p-SMAD2/3水平升高。在体内，sFgl2-MSCs显着改善肝功能，减少肝坏死面积，减少肿瘤坏死因子-α、白介素（IL）-1β和IL-6表达，增加IL-10表达，减少CD4 T和CD8 T肝脏浸润sFgl2基因修饰的MSCs通过促进Tregs分化、抑制Th17、Th1细胞分化，对Con A诱导的实验性AIH和可能代表 AIH 的临床治疗策略。© 2023。作者。

Autoimmune hepatitis (AIH) is a T-cell-mediated autoimmune liver disease that can lead to liver injury and has a poor long-term prognosis. Mesenchymal stromal cells (MSCs) have immunosuppressive effects and can treat AIH. CD4+ T cells express the unique inhibitory Fcγ receptor (FcγRIIB), which is the only receptor for the immunosuppressive factor soluble fibrinogen-like protein 2 (sFgl2). This study aimed to examine the therapeutic effect of sFgl2 gene-modified MSCs (sFgl2-MSCs) on AIH.MSCs were obtained from the inguinal fat of mice and cocultured with CD4+ T cells sorted from mouse spleens. FcγRIIB expression on CD4+ T cells was determined by flow cytometry. sFgl2 expression in MSCs transfected with lentiviral vectors carrying the Fgl2 gene and a green fluorescent protein-encoding sequence was determined by enzyme-linked immunosorbent assay. The percentages of Th1 cells Th17 cells and regulatory T cells (Tregs) were determined by flow cytometry And the levels of p-SHP2 and p-SMAD2/3 were detected by Western blotting after the cells were cocultured with MSCs for 72 h. After locating MSCs by in vivo imaging Con A-induced experimental AIH mice were randomly divided into 4 groups and administered different treatments. After 24 h histopathological scores liver function and cytokine levels were examined and the proportions of CD4+ T cells CD8+ T cells Tregs Th17 cells and Th1 cells in the spleen and liver were determined by flow cytometry. In addition immunohistochemical staining was used to detect the liver infiltration of T-bet-, Foxp3- and RORγ-positive cells.FcγRIIB expression on CD4+ T cells was upregulated after coculture with MSCs. After coculture with sFgl2-MSCs, the proportion of Tregs among CD4+ T cells increased, the proportion of Th17 and Th1 cells decreased, and the levels of p-SHP2 and p-SMAD2/3 increased. In vivo, sFgl2-MSCs significantly improved liver function, decreased liver necrosis area, decreased tumor necrosis factor-α, interleukin (IL)-1β and IL-6 expression, increased IL-10 expression, reduced liver infiltration of CD4+ T and CD8+ T cells, increased the proportion of Tregs and reduced the proportions of Th17 and Th1 cells in mice.By promoting Tregs differentiation and inhibiting Th17 and Th1 cell differentiation, sFgl2 gene-modified MSCs have a more powerful therapeutic effect on Con A-induced experimental AIH and may represent a strategy for the clinical treatment of AIH.© 2023. The Author(s).