Department of Rheumatology and Immunology, Peking University People's Hospital and Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis, Beijing, China.
Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, China.
Adv Exp Med Biol. 2024;1445:91-99. doi: 10.1007/978-981-97-0511-5_7.
Liver is the largest internal organ of the body with vital functions. In addition to its endocrine and exocrine activities, liver also plays a pivotal role in the immune system, including haematopoietic functions. Liver parenchymal cells, which are epithelial cells, have been found to possess innate immune functions by expressing pattern-recognition receptors (PRRs), producing complement components, and secreting cytokines. Intriguingly, in recent years, it has been discovered that liver epithelial cells also produce immunoglobulins (Igs), which have long been thought to be produced exclusively by B cells. Notably, even liver epithelial cells from B lymphocyte-deficient mice, including SCID mice and μMT mice, could also produce Igs. Compelling evidence has revealed both the physiological and pathological functions of liver-derived Igs. For instance, liver epithelial cells-derived IgM can serve as a source of natural and specific antibodies that contribute to innate immune responses, while liver-produced IgG can act as a growth factor to promote cell proliferation and survival in normal hepatocytes and hepatocarcinoma. Similar to that in B cells, the toll-like receptor 9 (TLR9)-MyD88 signaling pathway is also actively involved in promoting liver epithelial cells to secrete IgM. Liver-derived Igs could potentially serve as biomarkers, prognostic indicators, and therapeutic targets in the clinical setting, particularly for liver cancers and liver injury. Nevertheless, despite significant advances, much remains unknown about the mechanisms governing Ig transcription in liver cells, as well as the detailed functions of liver-derived Igs and their involvement in diseases and adaptive immunity. Further studies are still needed to reveal these underlying, undefined issues related to the role of liver-derived Igs in both immunity and diseases.
肝脏是人体最大的内脏器官，具有重要的功能。除了内分泌和外分泌功能外，肝脏在免疫系统中也起着关键作用，包括造血功能。肝实质细胞（上皮细胞）通过表达模式识别受体（PRRs）、产生补体成分和分泌细胞因子而具有先天免疫功能。有趣的是，近年来发现肝上皮细胞也能产生免疫球蛋白（Igs），而长期以来人们一直认为 Igs 仅由 B 细胞产生。值得注意的是，即使是缺乏 B 淋巴细胞的小鼠（包括 SCID 小鼠和 μMT 小鼠）的肝上皮细胞也能产生 Igs。有力的证据揭示了肝源性 Igs 的生理和病理功能。例如，肝上皮细胞衍生的 IgM 可以作为天然和特异性抗体的来源，有助于先天免疫反应，而肝产生的 IgG 可以作为生长因子促进正常肝细胞和肝癌细胞的增殖和存活。与 B 细胞相似，Toll 样受体 9（TLR9）-MyD88 信号通路也积极参与促进肝上皮细胞分泌 IgM。肝源性 Igs 可能在临床中作为生物标志物、预后指标和治疗靶点，特别是在肝癌和肝损伤方面。然而，尽管取得了显著进展，但肝细胞中 Ig 转录的调控机制以及肝源性 Igs 的详细功能及其在疾病和适应性免疫中的参与仍知之甚少。需要进一步的研究来揭示与肝源性 Igs 在免疫和疾病中的作用相关的这些尚未阐明的问题。
