Apicobasal Polarity Controls Lymphocyte Adhesion to Hepatic Epithelial Cells

作者：Reglero Real Natalia; Alvarez Varela Adrian; Cernuda Morollon Eva; Feito Jorge; Marcos Ramiro Beatriz; Fernandez Martin Laura; Jose Gomez Lechon Maria; Muntane Jordi; Sandoval Pilar; Majano Pedro L; Correas Isabel; Alonso Miguel A; Millan Jaime^*

来源：Cell Reports, 2014, 8(6): 1879-1893.

DOI：10.1016/j.celrep.2014.08.007

Loss of apicobasal polarity is a hallmark of epithelial pathologies. Leukocyte infiltration and crosstalk with dysfunctional epithelial barriers are crucial for the inflammatory response. Here, we show that apicobasal architecture regulates the adhesion between hepatic epithelial cells and lymphocytes. Polarized hepatocytes and epithelium from bile ducts segregate the intercellular adhesion molecule 1 (ICAM-1) adhesion receptor onto their apical, microvilli-rich membranes, which are less accessible by circulating immune cells. Upon cell depolarization, hepatic ICAM-1 becomes exposed and increases lymphocyte binding. Polarized hepatic cells prevent ICAM-1 exposure to lymphocytes by redirecting basolateral ICAM-1 to apical domains. Loss of ICAM-1 polarity occurs in human inflammatory liver diseases and can be induced by the inflammatory cytokine tumor necrosis factor alpha (TNF-alpha). We propose that adhesion receptor polarization is a parenchymal immune checkpoint that allows functional epithelium to hamper leukocyte binding. This contributes to the haptotactic guidance of leukocytes toward neigh boring damaged or chronically inflamed epithelial cells that expose their adhesion machinery.

• 出版日期2014-9-25