研究人员利用肝纤维化小鼠模型和人体组织来研究免疫适应性。肝纤维化迫使库普弗细胞（KC）失去与实质细胞的接触，下调了“KC特性”，从而使它们无法清除细菌。共生菌通过CD44刺激单核细胞被招募到空间上不同的血管区。其中，被招募的单核细胞形成了大量多核细胞（合胞体）聚集体，这些细胞表达表型KC标记，并显示出更强的细菌捕获能力。
合胞体通过CD36形成，并在人类肝硬化中被观察到，这可能是一种随着纤维化而演变的抗微生物防御。
据介绍，KC位于肝窦内，但会向实质细胞延伸假足以保持其特性，并充当人体的中央细菌过滤器。肝硬化极大地改变了血管结构，但KC如何适应尚不清楚。
附：英文原文
Title: Kupffer cell–like syncytia replenish resident macrophage function in the fibrotic liver
Author: Moritz Peiseler, Bruna Araujo David, Joel Zindel, Bas G. J. Surewaard, Woo-Yong Lee, Felix Heymann, Ysbrand Nusse, Fernanda V. S. Castanheira, Raymond Shim, Adrien Guillot, Alix Bruneau, Jawairia Atif, Catia Perciani, Christina Ohland, Priyanka Ganguli Mukherjee, Annika Niehrs, Roland Thuenauer, Marcus Altfeld, Mathias Amrein, Zhaoyuan Liu, Paul M. K. Gordon, Kathy McCoy, Justin Deniset, Sonya MacParland, Florent Ginhoux, Frank Tacke, Paul Kubes
Issue&Volume: 2023-09-08
Abstract: Kupffer cells (KCs) are localized in liver sinusoids but extend pseudopods to parenchymal cells to maintain their identity and serve as the body’s central bacterial filter. Liver cirrhosis drastically alters vascular architecture, but how KCs adapt is unclear. We used a mouse model of liver fibrosis and human tissue to examine immune adaptation. Fibrosis forced KCs to lose contact with parenchymal cells, down-regulating “KC identity,” which rendered them incapable of clearing bacteria. Commensals stimulated the recruitment of monocytes through CD44 to a spatially distinct vascular compartment. There, recruited monocytes formed large aggregates of multinucleated cells (syncytia) that expressed phenotypical KC markers and displayed enhanced bacterial capture ability. Syncytia formed via CD36 and were observed in human cirrhosis as a possible antimicrobial defense that evolved with fibrosis.
DOI: abq5202
Source: https://www.science.org/doi/full/10.1126/science.abq5202