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.

Descárgate este artículo aquí.
Más artículos en la revista SEBBM.

¿Acabas de publicar un artículo interesante?

Manda la referencia a través de nuestro formulario.  Límite de edad 32 años. Los artículos seleccionados serán destacados como artículos del mes y participarán en el Premio Fisher Scientific, que se entregará en el congreso de la SEBBM (inscripción y alojamiento gratuitos).

Otros "Artículos del mes"

Physical proximity of chromatin to nuclear pores prevents harmful R loop accumulation contributing to maintain genome stability

01-11-2017

During transcription, the mRNA may hybridize with DNA, forming an R loop, which can be physiological or pathological, constituting in this case a source of genomic instability. To understand the...

Leer más

Whi7 is an unstable cell-cycle repressor of the Start transcriptional program

01-10-2017

Start is the main decision point in eukaryotic cell cycle in which cells commit to a new round of cell division. It involves the irreversible activation of a transcriptional program...

Leer más

CTCF orchestrates the germinal centre transcriptional program and prevents premature plasma cell differentiation

01-09-2017

In germinal centres (GC) mature B cells undergo intense proliferation and immunoglobulin gene modification before they differentiate into memory B cells or long-lived plasma cells (PC). GC B-cell-to-PC transition involves...

Leer más

Catalytic Cycle of the N-Acetylglucosaminidase NagZ from Pseudomonas aeruginosa

01-08-2017

The N-acetylglucosaminidase NagZ of Pseudomonas aeruginosa catalyzes the first cytoplasmic step in recycling of muropeptides, cell-wall-derived natural products. This reaction regulates gene expression for the β-lactam resistance enzyme, β-lactamase. The...

Leer más

Crebbp loss cooperates with Bcl2 overexpression to promote lymphoma in mice.

01-07-2017

CREBBP is targeted by inactivating mutations in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Here, we provide evidence from transgenic mouse models that Crebbp deletion results in deficits...

Leer más

Local amplifiers of IL-4Rα-mediated macrophage activation promote repair in lung and liver

01-06-2017

The type 2 immune response controls helminth infection and maintains tissue homeostasis but can lead to allergy and fibrosis if not adequately regulated. We have discovered local tissue-specific amplifiers of...

Leer más

Programmed mitophagy is essential for the glycolytic switch during cell differentiation

01-05-2017

Retinal ganglion cells (RGCs) are the sole projecting neurons of the retina and their axons form the optic nerve. Here, we show that embryogenesis-associated mouse RGC differentiation depends on mitophagy...

Leer más

Bax transmembrane domain interacts with prosurvival Bcl-2 proteins in biological membranes

01-04-2017

The Bcl-2 (B-cell lymphoma 2) protein Bax (Bcl-2 associated X, apoptosis regulator) can commit cells to apoptosis via outer mitochondrial membrane permeabilization. Bax activity is controlled in healthy cells by...

Leer más

Histone chaperone activity of Arabidopsis thaliana NRP1 is blocked by cytochrome c

01-03-2017

Higher-order plants and mammals use similar mechanisms to repair and tolerate oxidative DNA damage. Most studies on the DNA repair process have focused on yeast and mammals, in which histone...

Leer más

The lipid sensor GPR120 promotes brown fat activation and FGF21 release from adipocytes

01-02-2017

The thermogenic activity of brown adipose tissue (BAT) and browning of white adipose tissue are important components of energy expenditure. Here we show that GPR120, a receptor for polyunsaturated fatty...

Leer más

Socios Protectores