Intrathymic laminin-mediated interactions: role in T cell migration and development
Intrathymic T cell differentiation is a key process for the development and maintenance of cell-mediated immunity, and occurs concomitantly to highly regulated migratory events. We have proposed a multivectorial model for describing intrathymic thymocyte migration. One of the individual vectors comp...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2015-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00579/full |
| _version_ | 1818253704614117376 |
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| author | Wilson eSavino DANIELLA AREAS MENDES-DA-CRUZ Daiane Cristina Ferreira Golbert Ingo eRiederer Vinicius eCotta-de-Almeida |
| author_facet | Wilson eSavino DANIELLA AREAS MENDES-DA-CRUZ Daiane Cristina Ferreira Golbert Ingo eRiederer Vinicius eCotta-de-Almeida |
| author_sort | Wilson eSavino |
| collection | DOAJ |
| description | Intrathymic T cell differentiation is a key process for the development and maintenance of cell-mediated immunity, and occurs concomitantly to highly regulated migratory events. We have proposed a multivectorial model for describing intrathymic thymocyte migration. One of the individual vectors comprises interactions mediated by laminins, a heterotrimeric protein family of the extracellular matrix. Several laminins are expressed in the thymus, being produced by microenvironmental cells, particularly thymic epithelial cells. Also, thymocytes and epithelial cells express integrin-type laminin receptors. Functionally, it has been reported that the dy/dy mutant mouse (lacking the laminin isoform 211) exhibits defective thymocyte differentiation. Several data show haptotactic effects of laminins upon thymocytes, as well as their adhesion on thymic epithelial cells; both effects being prevented by anti-laminin or anti-laminin receptor antibodies. Interestingly, laminin synergizes with chemokines to enhance thymocyte migration, whereas classe-3 semaphorins and B ephrins, which exhibit chemorepulsive effects in the thymus, downregulate laminin-mediated migratory responses of thymocytes. More recently, we showed that knocking down the ITGA6 gene (which encodes the α6 integrin chain of laminin receptors) in human thymic epithelial cells, modulates a large number of cell-migration related genes, and results in changes of adhesion pattern of thymocytes onto the thymic epithelium. Overall, laminin-mediated interactions can be placed at the cross-road of the multivectorial process of thymocyte migration, with a direct influence per se, as well as by modulating other molecular interactions associated with the intrathymic trafficking events. |
| first_indexed | 2024-12-12T16:44:18Z |
| format | Article |
| id | doaj.art-42a1a9d197d340da8b4ae95b545e89b9 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T16:44:18Z |
| publishDate | 2015-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-42a1a9d197d340da8b4ae95b545e89b92022-12-22T00:18:29ZengFrontiers Media S.A.Frontiers in Immunology1664-32242015-11-01610.3389/fimmu.2015.00579164692Intrathymic laminin-mediated interactions: role in T cell migration and developmentWilson eSavino0DANIELLA AREAS MENDES-DA-CRUZ1Daiane Cristina Ferreira Golbert2Ingo eRiederer3Vinicius eCotta-de-Almeida4Fiocruz - Fundação Oswaldo CruzFiocruz - Fundação Oswaldo CruzFiocruz - Fundação Oswaldo CruzFiocruz - Fundação Oswaldo CruzFiocruz - Fundação Oswaldo CruzIntrathymic T cell differentiation is a key process for the development and maintenance of cell-mediated immunity, and occurs concomitantly to highly regulated migratory events. We have proposed a multivectorial model for describing intrathymic thymocyte migration. One of the individual vectors comprises interactions mediated by laminins, a heterotrimeric protein family of the extracellular matrix. Several laminins are expressed in the thymus, being produced by microenvironmental cells, particularly thymic epithelial cells. Also, thymocytes and epithelial cells express integrin-type laminin receptors. Functionally, it has been reported that the dy/dy mutant mouse (lacking the laminin isoform 211) exhibits defective thymocyte differentiation. Several data show haptotactic effects of laminins upon thymocytes, as well as their adhesion on thymic epithelial cells; both effects being prevented by anti-laminin or anti-laminin receptor antibodies. Interestingly, laminin synergizes with chemokines to enhance thymocyte migration, whereas classe-3 semaphorins and B ephrins, which exhibit chemorepulsive effects in the thymus, downregulate laminin-mediated migratory responses of thymocytes. More recently, we showed that knocking down the ITGA6 gene (which encodes the α6 integrin chain of laminin receptors) in human thymic epithelial cells, modulates a large number of cell-migration related genes, and results in changes of adhesion pattern of thymocytes onto the thymic epithelium. Overall, laminin-mediated interactions can be placed at the cross-road of the multivectorial process of thymocyte migration, with a direct influence per se, as well as by modulating other molecular interactions associated with the intrathymic trafficking events.http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00579/fullExtracellular MatrixIntegrinsThymusthymic epithelial cellsChemokines.T-cell development |
| spellingShingle | Wilson eSavino DANIELLA AREAS MENDES-DA-CRUZ Daiane Cristina Ferreira Golbert Ingo eRiederer Vinicius eCotta-de-Almeida Intrathymic laminin-mediated interactions: role in T cell migration and development Frontiers in Immunology Extracellular Matrix Integrins Thymus thymic epithelial cells Chemokines. T-cell development |
| title | Intrathymic laminin-mediated interactions: role in T cell migration and development |
| title_full | Intrathymic laminin-mediated interactions: role in T cell migration and development |
| title_fullStr | Intrathymic laminin-mediated interactions: role in T cell migration and development |
| title_full_unstemmed | Intrathymic laminin-mediated interactions: role in T cell migration and development |
| title_short | Intrathymic laminin-mediated interactions: role in T cell migration and development |
| title_sort | intrathymic laminin mediated interactions role in t cell migration and development |
| topic | Extracellular Matrix Integrins Thymus thymic epithelial cells Chemokines. T-cell development |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2015.00579/full |
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