原发性胆汁性胆管炎(PBC)以肝内破坏性小叶间胆管炎和血清抗线粒体抗体(AMA)为特征。髓系细胞[单核细胞/巨噬细胞、树突细胞、髓系源性抑制细(MDSCs)]在PBC肝内免疫微环境中扮演关键角色。我们的前期研究表明，不成熟髓系细胞MDSCs可作为负性调控细胞抑制肝内过度活化的T细胞反应。同时，我们的GWAS研究发现了转录因子ARID3a基因区域SNP位点显著提高PBC易感性，而ARID3a参与B细胞的发育和功能。由于ARID3a也在髓系细胞中表达，因此，非常有必要探索ARID3a在髓系细胞尤其是MDSCs发育中的作用。我们假设，转录因子ARID3a可能作为免疫检查点决定髓系细胞的发育和功能，调控ARID3a的表达可能显著影响不成熟(MDSCs)和成熟髓系细胞(巨噬细胞和DCs等)之间的平衡，从而恢复肝脏免疫稳态。我们的研究有助于阐明”肝-骨轴”在PBC发病机制中的作用，探索潜在免疫治疗靶点

Primary biliary cholangitis (PBC) is characterized by the destructive interlobular cholangitis in histology and anti-mitochodrial antibody (AMA) in serum, resulting from the interaction between the susceptible genes and environmental factors. Myeloid cells (including macrophage/monocytes, dendritic cells， myeloid-derived suppressor cells) play vital roles in the hepatic immune microenvironment of PBC. As a special population of immature myeloid cells, myeloid-derived suppressor cells (MDSCs) play a critical role in maintaining the immunohemostasis in autoimmune disease. Our preliminary study showed that numbers and suppression function of MDSCs were significantly elevated in the peripheral blood and liver tissues of PBC compared with healthy controls, suggesting that MDSCs may serve as a negative regulator of excessive T-cell responses in the liver. Most recently, our GWAS study showed that SNP of transcription factor ARID3a gene loci were associated with the susceptiblity of Chinese PBC, while ARID3a was reported to be involved in the development and function of B cells. Since ARID3a expression was detected in myeloid cells in PBC patients, it is very interesting to explore the potential roles of ARID3a in the development of myeloid cells especially MDSCs. We hypothesize that ARID3a may serve as an immune checkpoint in the fate of myeloid cells, modulating the expression of ARID3a may markedly affect the balance between immature myeloid cells (MDSCs) and mature myeloid cells (macrophage and DCs), resulting in the recovery of immunohomeostasis in the liver. Our study may elucidate the role of Liver-Bone axis in the pathogenesis of PBC, and explore the promising immunotherapy strategy in autoimmune liver diseases.