Laminin-211 controls thymocyte—thymic epithelial cell interactions

Ocampo, J.S.P.; Brito, José M.; Correa-de-Santana, Eliane; Borojević, Radovan; Villa‐Verde, Déa Maria Serra; Savino, Wilson

doi:10.1016/j.cellimm.2008.06.005

Cited by 21 publications

(25 citation statements)

References 35 publications

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“…Despite VLA-6 also had dropped, the laminin density stain had a significant increase in diabetic mice. Laminin plays an important role in thymocyte migration and high levels of this molecule are connected with higher migration rates (Ocampo et al, 2008;Smaniotto et al, 2005). However, we did not find significant changes in the ex-vivo transmigration assay using laminin or laminin plus CXCL12 for membrane coating, as it An intense decrease of specific messenger RNA for CCL25 and CXCL12 was observed in the thymus from diabetic mice.…”

Section: Discussioncontrasting

confidence: 74%

“…However, few studies in the literature suggest that the expression of laminin or other ECM elements are controlled by the same hormones (Ocampo et al, 2008;Gruver and Sempowski, 2008). Although we have not measured intrathymic migration in this study, our results suggest that changes in ECM do alter intrathymic migration with important consequences for T cell maturation.…”

Section: Discussioncontrasting

confidence: 60%

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Thymic microenvironmental alterations in experimentally induced diabetes

et al. 2010

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Section: Discussioncontrasting

confidence: 74%

Section: Discussioncontrasting

confidence: 60%

Thymic microenvironmental alterations in experimentally induced diabetes

et al. 2010

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“…Moreover, we investigated the expression and in situ localization of laminin chains in the human thymic tissue, as well as in the lymphoepithelial complex named thymic nurse cells. Also, we showed that TEC produce laminin and grows faster in the presence of this molecule in culture dishes [12,13]. …”

Section: Introductionmentioning

confidence: 99%

ITGA6 gene silencing by RNA interference modulates the expression of a large number of cell migration-related genes in human thymic epithelial cells

et al. 2013

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BackgroundThe thymic epithelium is the major microenvironmental component of the thymus, the primary lymphoid organ responsible for the generation of T lymphocytes. Thymic epithelial cells (TEC) control intrathymic T cell differentiation by means of distinct types of interactions. TEC constitutively produce chemokines and extracellular matrix ligands (such as laminin and fibronectin) and express corresponding receptors, which allow thymocytes to migrate in a very ordered fashion. We previously showed that laminin mediates TEC/thymocyte interactions in both mice and humans. More recently, we used RNAi technology to knock-down the ITGA5 gene (which encodes CD49e, the integrin α-chain subunit of the fibronectin receptor VLA-5) in cultured human TEC. Using a similar strategy, herein we knocked-down the ITGA6 gene, which encodes CD49f, the α-chain of two integrin-type laminin receptors, namely VLA-6 (α6β1) and α6β4.ResultsWe first confirmed that RNAi-induced knock-down of the ITGA6 gene was successful, at both transcription and translational levels, with a significant decrease in the membrane expression of CD49f, apart from CD49b, CD49c and CD49d, ascertained by cytofluorometry on living TEC. We also demonstrated that such knock-down promotes a decrease in cell adhesion to laminin. Using quantitative PCR, we demonstrated that gene expression of other integrin α-chains were concomitantly down-regulated, particularly those which form other laminin receptors, including ITGA1, ITGA2 and ITGA7. Interestingly enough, LAMA1 gene expression (whose corresponding protein chain is part of laminin-111) was largely increased in ITGA6 knocked-down TEC cultures. Lastly, the network complexity of gene expression under ITGA6 influence is much broader, since we found that other cell migration-related genes, namely those coding for various chemokines, are also modulated when IGTA6 is knocked-down.ConclusionThe data presented herein clearly show that down regulation of ITGA6 gene in the human thymic epithelium triggers a complex cascade of effects upon the expression levels of several other cell migration-related genes, including extracellular matrix and chemokine ligands and receptors. Taken together, these data unravel the concept that the expression of genes involved in controlling of thymocyte migration by the thymic microenvironment should be regarded as complex networks, so that a defect in the expression of one single gene may reflect in an amplified cascade with functional consequences for TEC adhesion onto the natural ligand and potential consequences upon the normal patterns of TEC/thymocyte interactions.

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“…TNCs can express lysosomal-specific molecules and different proteases involved in the peptide/major histocompatibility complex (MHC) molecules—MHC class I and MHC class II—presentation. In human TNCs, laminin 211 has been detected [53], which is essential for the binding of these epithelial cells to immature T lymphocytes and in releasing T lymphocytes from the TNC vacuoles. Some TNCs also express the epithelial stem cell phenotype-associated transcription factor Trp-63 [51] and are K5+K8+ cells, suggesting that TNCs also possess different stages of development.…”

Section: Introductionmentioning

confidence: 99%

The Importance of the Nurse Cells and Regulatory Cells in the Control of T Lymphocyte Responses

García

Tamayó

2013

BioMed Research International

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T lymphocytes from the immune system are bone marrow-derived cells whose development and activities are carefully supervised by two sets of accessory cells. In the thymus, the immature young T lymphocytes are engulfed by epithelial “nurse cells” and retained in vacuoles, where most of them (95%) are negatively selected and removed when they have an incomplete development or express high affinity autoreactive receptors. The mature T lymphocytes that survive to this selection process leave the thymus and are controlled in the periphery by another subpopulation of accessory cells called “regulatory cells,” which reduce any excessive immune response and the risk of collateral injuries to healthy tissues. By different times and procedures, nurse cells and regulatory cells control both the development and the functions of T lymphocyte subpopulations. Disorders in the T lymphocytes development and migration have been observed in some parasitic diseases, which disrupt the thymic microenvironment of nurse cells. In other cases, parasites stimulate rather than depress the functions of regulatory T cells decreasing T-mediated host damages. This paper is a short review regarding some features of these accessory cells and their main interactions with T immature and mature lymphocytes. The modulatory role that neurotransmitters and hormones play in these interactions is also revised.

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Laminin-211 controls thymocyte—thymic epithelial cell interactions

Cited by 21 publications

References 35 publications

Thymic microenvironmental alterations in experimentally induced diabetes

Thymic microenvironmental alterations in experimentally induced diabetes

ITGA6 gene silencing by RNA interference modulates the expression of a large number of cell migration-related genes in human thymic epithelial cells

The Importance of the Nurse Cells and Regulatory Cells in the Control of T Lymphocyte Responses

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