Nature communications · 2023
Unique DUOX2+ACE2+ small cholangiocytes are pathogenic targets for primary biliary cholangitis.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Li Xi, Li Yan, Xiao Jintao, Wang Huiwen, Guo Yan, Mao Xiuru, Shi Pan, Hou Yanliang, Zhang Xiaoxun, Zhao Nan, Zheng Minghua, He Yonghong, Ding Jingjing, Tan Ya, Liao Min, Li Ling, Peng Ying, Li Xuan, Pan Qiong, Xie Qiaoling, Li Qiao, Li Jianwei, Li Ying, Chen Zhe, Huang Yongxiu, Assis David N, Cai Shi-Ying, Boyer James L, Huang Xuequan, Tang Can-E, Liu Xiaowei, Peng Shifang, Chai Jin
Аннотация
Cholangiocytes play a crucial role in bile formation. Cholangiocyte injury causes cholestasis, including primary biliary cholangitis (PBC). However, the etiology of PBC remains unclear despite being characterized as an autoimmune disease. Using single-cell RNA sequencing (scRNA-seq), fluorescence-activated-cell-sorting, multiplex immunofluorescence (IF) and RNAscope analyses, we identified unique DUOX2+ACE2+ small cholangiocytes in human and mouse livers. Their selective decrease in PBC patients was associated with the severity of disease. Moreover, proteomics, scRNA-seq, and qPCR analyses indicated that polymeric immunoglobulin receptor (pIgR) was highly expressed in DUOX2+ACE2+ cholangiocytes. Serum anti-pIgR autoantibody levels were significantly increased in PBC patients, regardless of positive and negative AMA-M2. Spatial transcriptomics and multiplex IF revealed that CD27+ memory B and plasma cells accumulated in the hepatic portal tracts of PBC patients. Collectively, DUOX2+ACE2+ small cholangiocytes are pathogenic targets in PBC, and preservation of DUOX2+ACE2+ cholangiocytes and targeting anti-pIgR autoantibodies may be valuable strategies for therapeutic interventions in PBC.