Apicobasal polarity controls lymphocyte adhesion to hepatic epithelial cells
10.1016/j.celrep.2014.08.007Cell Reports 8 (2014): 1879–1893
Funded byThis work was supported by grants SAF2011-22624 (to J.M.), BFU2012-32532 and CSD2009-00016 (to M.A.A.), and BFU2011- 22859 (to I.C.) from the Ministerio de Ciencia e Innovación; grant S2010/ BMD-2305 from Comunidad de Madrid; and grant FIS PI10/00101 from the Ministerio Sanidad and Fundacio n Mutua Madrileña (to P.L.). N.R. is a recipient of a JAE predoctoral fellowship from the CSIC. B.M. is a recipient of an FPI fellowship from the MINECO
ProjectComunidad de Madrid. S2010/BMD-2305/CS INTERATOMICS
SubjectsApicobasal; ICAM-1; Epithelial cells; Biología y Biomedicina / Biología
Rights© 2014 The Authors
Esta obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional.
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-a). 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 neighboring damaged or chronically inflamed epithelial cells that expose their adhesion machinery
Google Scholar:Reglero-Real, Natalia - Álvarez-Varela, Adrián - Cernuda-Morollón, Eva - Feito, Jorge - Marcos-Ramiro, Beatriz - Fernández-Martín, Laura - Gómez-Lechón, Maria José - Muntané, Jordi - Sandoval, Pilar - Majano, Pedro L. - Correas Hornero, María Isabel - Alonso, Miguel A. - Millán, Jaime
This item appears in the following Collection(s)
Showing items related by title, author, creator and subject.