多聚免疫球蛋白受体通过STAT3通路调节白细胞介素-17信号通路并预防自身免疫性肝炎

Ting Li; Tongtong Pan; Nannan Zheng; Xiong Ma; Xiaodong Wang; Fang Yan; Huimian Jiang; Yuxin Wang; Hongwei Lin; Jing Lin; Huadong Zhang; Jia Huang; Lingming Kong; Anmin Huang; Qingxiu Liu; Yongping Chen; Dazhi Chen

doi:10.1016/j.eng.2024.01.006

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工程（英文） ›› 2024, Vol. 36 ›› Issue (5) : 209-222. DOI: 10.1016/j.eng.2024.01.006

研究论文

Article

多聚免疫球蛋白受体通过STAT3通路调节白细胞介素-17信号通路并预防自身免疫性肝炎

Ting Li ^a^,^b ,
Tongtong Pan ^a^,^* ,
Nannan Zheng ^a ,
Xiong Ma ^c ,
Xiaodong Wang ^a ,
Fang Yan ^a ,
Huimian Jiang ^a ,
Yuxin Wang ^a ,
Hongwei Lin ^a ,
Jing Lin ^a ,
Huadong Zhang ^a ,
Jia Huang ^a ,
Lingming Kong ^d ,
Anmin Huang ^d ,
Qingxiu Liu ^e ,
Yongping Chen ^a^,^* ,
Dazhi Chen ^*

作者信息 +

STAT3-Dependent Effects of Polymeric Immunoglobulin Receptor in Regulating Interleukin-17 Signaling and Preventing Autoimmune Hepatitis

Ting Li ^a^,^b^,^- ,
Tongtong Pan ^a^,^-^,^* ,
Nannan Zheng ^a ,
Xiong Ma ^c ,
Xiaodong Wang ^a ,
Fang Yan ^a ,
Huimian Jiang ^a ,
Yuxin Wang ^a ,
Hongwei Lin ^a ,
Jing Lin ^a ,
Huadong Zhang ^a ,
Jia Huang ^a ,
Lingming Kong ^d ,
Anmin Huang ^d ,
Qingxiu Liu ^e ,
Yongping Chen ^a^,^* ,
Dazhi Chen ^*

Author information +

History +

Abstract

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.

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Keywords

Autoimmune hepatitis / Polymeric immunoglobulin receptor / Regenerating islet-derived 3 beta / Intestinal microbiota / Signal transducer and activator of transcription 3

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Ting Li, Tongtong Pan, Nannan Zheng. 多聚免疫球蛋白受体在调节白细胞介素-17信号传导和预防自身免疫性肝炎中的STAT3依赖性作用. Engineering. 2024, 36(5): 209-222 https://doi.org/10.1016/j.eng.2024.01.006

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