Dataset Information

Control of alpha4beta7 integrin expression and CD4 T cell homing by the beta1 integrin subunit.

ABSTRACT: The alpha4beta7 integrin promotes homing of T cells to intestinal sites. The alpha4 integrin subunit that pairs with beta7 integrin can also pair with beta1 integrin. In this paper, we show that the preferential pairing of beta1 integrin with alpha4 integrin regulates the expression of alpha4beta7 on T cells. In the absence of beta1 integrin, naive mouse CD4 T cells have increased alpha4beta7 expression, resulting in increased adhesion to mucosal addressin cell adhesion molecule-1 and enhanced homing to Peyer's patches (PP). In a reciprocal manner, overexpression of beta1 integrin causes the loss of alpha4beta7 expression and decreased homing to PP. A similar upregulation of beta1 integrin and suppression of alpha4beta7 expression occurs rapidly after CD4 T cell activation. beta1 integrin thus dominates beta7 integrin for alpha4 integrin pairing, thereby controlling the abundance of unpaired alpha4 integrin. Increasing the abundance of alpha4 integrin relative to beta1 integrin is critical to retinoic acid-mediated expression of alpha4beta7 integrin during T cell activation. In the absence of beta1 integrin, endogenous Ag-specific CD4 T cells uniformly express high levels of alpha4beta7 after Listeria monocytogenes infection. The resulting beta1-deficient early memory T cells have decreased localization to the bone marrow and enhanced localization to PP after infection. Thus, the preferential association of beta1 integrin with alpha4 integrin suppresses alpha4beta7 integrin expression and regulates the localization of memory CD4 T cells.

SUBMITTER: DeNucci CC

PROVIDER: S-EPMC2824783 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Control of alpha4beta7 integrin expression and CD4 T cell homing by the beta1 integrin subunit.

DeNucci Christopher C CC Pagán Antonio J AJ Mitchell Jason S JS Shimizu Yoji Y

Journal of immunology (Baltimore, Md. : 1950) 20100129 5

The alpha4beta7 integrin promotes homing of T cells to intestinal sites. The alpha4 integrin subunit that pairs with beta7 integrin can also pair with beta1 integrin. In this paper, we show that the preferential pairing of beta1 integrin with alpha4 integrin regulates the expression of alpha4beta7 on T cells. In the absence of beta1 integrin, naive mouse CD4 T cells have increased alpha4beta7 expression, resulting in increased adhesion to mucosal addressin cell adhesion molecule-1 and enhanced h ...[more]

PMID: 20118278

Similar Datasets

Project description:During embryogenesis, the neural stem cells (NSC) of the developing cerebral cortex are located in the ventricular zone (VZ) lining the cerebral ventricles. They exhibit apical and basal processes that contact the ventricular surface and the pial basement membrane, respectively. This unique architecture is important for VZ physical integrity and fate determination of NSC daughter cells. In addition, the shorter apical process is critical for interkinetic nuclear migration (INM), which enables VZ cell mitoses at the ventricular surface. Despite their importance, the mechanisms required for NSC adhesion to the ventricle are poorly understood. We have shown previously that one class of candidate adhesion molecules, laminins, are present in the ventricular region and that their integrin receptors are expressed by NSC. However, prior studies only demonstrate a role for their interaction in the attachment of the basal process to the overlying pial basement membrane. Here we use antibody-blocking and genetic experiments to reveal an additional and novel requirement for laminin/integrin interactions in apical process adhesion and NSC regulation. Transient abrogation of integrin binding and signalling using blocking antibodies to specifically target the ventricular region in utero results in abnormal INM and alterations in the orientation of NSC divisions. We found that these defects were also observed in laminin alpha2 deficient mice. More detailed analyses using a multidisciplinary approach to analyse stem cell behaviour by expression of fluorescent transgenes and multiphoton time-lapse imaging revealed that the transient embryonic disruption of laminin/integrin signalling at the VZ surface resulted in apical process detachment from the ventricular surface, dystrophic radial glia fibers, and substantial layering defects in the postnatal neocortex. Collectively, these data reveal novel roles for the laminin/integrin interaction in anchoring embryonic NSCs to the ventricular surface and maintaining the physical integrity of the neocortical niche, with even transient perturbations resulting in long-lasting cortical defects.

Dataset Information

Control of alpha4beta7 integrin expression and CD4 T cell homing by the beta1 integrin subunit.

Publications

Control of alpha4beta7 integrin expression and CD4 T cell homing by the beta1 integrin subunit.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets