Schildberg Frank A, Sharpe Arlene H, Turley Shannon J
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Curr Opin Immunol. 2015 Feb;32:1-6. doi: 10.1016/j.coi.2014.10.002. Epub 2014 Oct 28.
A metabolic organ, the liver also has a central role in tolerance induction. Stromal cells lining the hepatic sinusoids, such as liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs), are the first liver cells to encounter gut-derived and systemic antigens, thereby shaping local and systemic tolerance. Recent studies have demonstrated that stromal cells can modulate immune responses by antigen-dependent and independent mechanisms. Stromal cells interfere with the function of other antigen-presenting cells (APCs) and induce non-responsive T cells as well as regulatory T cells and myeloid-derived suppressor cells (MDSCs). The immunosuppressive microenvironment thus created provides a means to protect the liver from tissue damage. Such tolerized surroundings, however, can be exploited by certain pathogens, promoting persistent liver infections.
肝脏作为一个代谢器官，在免疫耐受诱导中也起着核心作用。肝血窦内衬的基质细胞，如肝窦内皮细胞（LSECs）和肝星状细胞（HSCs），是最早接触肠道来源和全身抗原的肝细胞，从而塑造局部和全身的免疫耐受。最近的研究表明，基质细胞可以通过抗原依赖和非依赖机制调节免疫反应。基质细胞干扰其他抗原呈递细胞（APC）的功能，并诱导无反应性T细胞以及调节性T细胞和髓系来源的抑制细胞（MDSC）。由此产生的免疫抑制微环境为保护肝脏免受组织损伤提供了一种手段。然而，某些病原体可以利用这种耐受环境，导致肝脏持续感染。
