One-third of patients with autoimmune hepatitis (AIH) have cirrhosis at the time of diagnosis. The relevance of these variables, although unknown, is believed to be critical in AIH because of suspected interactions between the gut microbiome and genetic factors. Dysbiosis of the gut flora and elevated polymeric immunoglobulin receptor (pIgR) levels have been observed in both patients and mouse models. Moreover, there is a direct relationship between pIgR expression and transaminase levels in patients with AIH. In this study, we aimed to explore how pIgR influences the secretion of regenerating islet-derived 3 beta (Reg3b) and the flora composition in AIH using in vivo experiments involving patients with AIH and a concanavalin A-induced mouse model of AIH. Reg3b expression was reduced in pIgR gene (Pigr)-knockout mice compared to that in wild-type mice, leading to increased microbiota disruption. Conversely, exogenous pIgR supplementation increased Reg3b expression and maintained microbiota homeostasis. RNA sequencing revealed the participation of the interleukin (IL)-17 signaling pathway in the regulation of Reg3b through pIgR. Furthermore, the introduction of external pIgR could not restore the imbalance in gut microbiota in AIH, and the decrease in Reg3b expression was not apparent following the inhibition of signal transducer and activator of transcription 3 (STAT3). In this study, pIgR facilitated the upregulation of Reg3b via the STAT3 pathway, which plays a crucial role in preserving the balance of the intestinal microbiota in AIH. Through this research, we discovered new molecular targets that can be used for the diagnosis and treatment of AIH.

三分之一的自身免疫性肝炎（AIH）患者在诊断时已患有肝硬化。这些变量的相关性虽然未知，但由于肠道微生物组与遗传因素之间的相互作用被怀疑，因此被认为在 AIH 中至关重要。在患者和小鼠模型中均观察到肠道菌群失调和聚合免疫球蛋白受体 (pIgR) 水平升高。此外，AIH 患者的 pIgR 表达与转氨酶水平之间存在直接关系。在本研究中，我们旨在通过涉及 AIH 患者和伴刀豆球蛋白 A 诱导的 AIH 小鼠模型的体内实验，探讨 pIgR 如何影响再生胰岛源性 3β (Reg3b) 的分泌和 AIH 中的菌群组成。与野生型小鼠相比， pIgR 基因 ( Pigr ) 敲除小鼠的 Reg3b 表达降低，导致微生物群破坏增加。相反，补充外源性 pIgR 会增加 Reg3b 表达并维持微生物群稳态。RNA测序揭示了白细胞介素(IL)-17信号通路通过pIgR参与Reg3b的调节。此外，引入外部pIgR并不能恢复AIH肠道菌群的失衡，并且抑制信号转导和转录激活子3（STAT3）后Reg3b表达的下降并不明显。在这项研究中，pIgR 通过 STAT3 途径促进 Reg3b 的上调，这在维持 AIH 肠道微生物群的平衡方面发挥着至关重要的作用。通过这项研究，我们发现了可用于AIH诊断和治疗的新分子靶点。