| First Author | Iacovelli S | Year | 2009 |
| Journal | PLoS One | Volume | 4 |
| Issue | 10 | Pages | e7586 |
| PubMed ID | 19851463 | Mgi Jnum | J:154039 |
| Mgi Id | MGI:4367133 | Doi | 10.1371/journal.pone.0007586 |
| Citation | Iacovelli S, et al. (2009) Lymphoid EVA1 expression is required for DN1-DN3 thymocytes transition. PLoS One 4(10):e7586 |
| abstractText | BACKGROUND: Thymus organogenesis and T lymphocyte development are accomplished together during fetal life. Proper development and maintenance of thymus architecture depend on signals generated by a sustained crosstalk between developing thymocytes and stromal elements. Any maturation impairment occurring in either cellular component leads to an aberrant thymic development. Gene expression occurring during T lymphocyte differentiation must be coordinated in a spatio-temporal fashion; one way in which this is achieved is through the regulation by cell-cell adhesion and interactions. PRINCIPAL FINDINGS: We examined the role played by Epithelial V-like Antigen 1 (EVA1), an Ig adhesion molecule expressed on thymus epithelial cells (TEC) and immature thymocytes, in T cell development by employing RNA interference in vitro and in vivo models. Fetal liver derived haematopoietic progenitors depleted of Eva1, displayed a delayed DN1-DN3 transition and failed to generate CD4CD8 double positive T cells in OP9-DL1 coculture system. In addition, we could observe a coordinated Eva1 up-regulation in stromal and haematopoietic cells in coculture control experiments, suggesting a possible EVA1 involvement in TEC-haematopoietic cells crosstalk mechanisms. Similarly, Rag2-gamma c double knock out mice, transplanted with Eva1 depleted haematopoietic progenitors displayed a 10-fold reduction in thymus reconstitution and a time delayed thymocytes maturation compared to controls. CONCLUSIONS: Our findings show that modulation of Eva1 expression in thymocytes is crucial for lymphocyte physiological developmental progression and stromal differentiation. |
