Liver Immune Profiling Reveals Pathogenesis and Therapeutics for Biliary Atresia

应用领域

Biliary atresia (BA) is a severe cholangiopathy that leads to liver failure in infants, but its pathogenesis remains to be fully characterized. By single-cell RNA profiling, we observed macrophage hypo-inflammation, Kupffer cell scavenger function defects, cytotoxic T cell expansion, and deficiency of CX3CR1⁺effector T and natural killer (NK) cells in infants with BA. More importantly, we discovered that hepatic B cell lymphopoiesis did not cease after birth and that tolerance defects contributed to immunoglobulin G (IgG)-autoantibody accumulation in BA. In a rhesus-rotavirus induced BA model, depleting B cells or blocking antigen presentation ameliorated liver damage. In a pilot clinical study, we demonstrated that rituximab was effective in depleting hepatic B cells and restoring the functions of macrophages, Kupffer cells, and T cells to levels comparable to those of control subjects. In summary, our comprehensive immune profiling in infants with BA had educed that B-cell-modifying therapies may alleviate liver pathology.

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基因水平：PCR Array、RT-PCR、PCR、单细胞测序
蛋白水平：MSD、Luminex、CBA、Elispot、Antibody Array、ELISA、Sengenics
细胞水平：细胞染色、细胞分选、细胞培养、细胞功能
组织水平：空间多组学、多重荧光免疫组化、免疫组化、免疫荧光
数据分析：流式数据分析、组化数据分析、多因子数据分析

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