enero15Referencia

Cell Reports, 2014, Volume 8, Issue 6, p1879–1893

Autores

Natalia Reglero-Real, Adrián Álvarez-Varela, Eva Cernuda-Morollón, Jorge Feito, Beatriz Marcos-Ramiro, Laura Fernández-Martín, Maria José Gómez-Lechón, Jordi Muntané, Pilar Sandoval, Pedro L. Majano, Isabel Correas, Miguel A. Alonso, Jaime Millán

Resumen

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-α). 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.

Descripción

Las células epiteliales establecen una polaridad apicobasal para llevar a cabo sus funciones de barrera, protección y filtración. Una característica común en las patologías epiteliales es que las células pierden esta morfología polarizada. En este trabajo hemos demostrado que el grado de polarización apicobasal de células epiteliales hepáticas regula su capacidad para interaccionar con los linfocitos T. Esto ocurre porque las células polarizadas y sanas segregan en su dominio apical, menos accesible a las células del sistema inmunitario, su principal receptor de adhesión linfocitaria, ICAM-1, previniendo la unión de células inmunitarias. Cuando se pierde la polaridad apicobasal, ICAM-1 se dispersa del dominio apical, se expone, y es reconocido por los linfocitos T.

grupo

REFERENCIA DEL GRUPO INVESTIGADOR

El grupo de biología celular de la inflamación del Centro de Biología Molecular Severo Ochoa se creo en 2009 para estudiar los aspectos celulares de la respuesta inmunitaria. El grupo está dirigido pro el científico del CSIC Jaime Millán y estudia las disfunciones que citoquinas inflamatorias causan en las barreras en endoteliales y epiteliales, con especial énfasis en los mecanismos de transporte intracelular que intervienen en dichas alteraciones. El artículo seleccionado forma parte del trabajo de doctorado de Natalia Reglero-Real, primera tesis doctoral del grupo. La Dra. Reglero-Real trabaja actualmente como investigadora postdoctoral en el William Harvey Research Institute, en Londres.

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