title: EphB2 and EphB3 play an important role in the lymphoid seeding of murine adult thymus.
abstract: Adult thymuses lacking either ephrin type B receptor 2 (EphB2) or EphB3, or expressing a truncated form of EphB2, the forward signal-deficient EphB2LacZ, have low numbers of early thymic progenitors (ETPs) and are colonized in vivo by reduced numbers of injected bone marrow (BM) lineage-negative (Lin(-)) cells. Hematopoietic progenitors from these EphB mutants showed decreased capacities to colonize wild type (WT) thymuses compared with WT precursors, with EphB2(-/-) cells exhibiting the greatest reduction. WT BM Lin(-) cells also showed decreased colonizing capacity into mutant thymuses. The reduction was also more severe in EphB2(-/-) host thymuses, with a less severe phenotype in the EphB2LacZ thymus. These results suggest a major function for forward signaling through EphB2 and, to a lesser extent, EphB3, in either colonizing progenitor cells or thymic stromal cells, for in vivo adult thymus recruitment. Furthermore, the altered expression of the molecules involved in thymic colonization that occurs in the mutant thymus correlates with the observed colonizing capacities of different mutant mice. Reduced production of CCL21 and CCL25 occurred in the thymus of the 3 EphB-deficient mice, but their expression, similar to that of P-selectin, on blood vessels, the method of entry of progenitor cells into the vascular thymus, only showed a significant reduction in EphB2(-/-) and EphB3(-/-) thymuses. Decreased migration into the EphB2(-/-) thymuses correlated also with reduced expression of both ephrinB1 and ephrinB2, without changes in the EphB2LacZ thymuses. In the EphB3(-/-) thymuses, only ephrinB1 expression appeared significantly diminished, confirming the relevance of forward signals mediated by the EphB2-ephrinB1 pair in cell recruitment into the adult thymus.
authors: *Department of Cell Biology, Faculty of Biology, Complutense University of Madrid, Madrid, Spain; Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil; Pediatric Hematology and Oncology Program, Research Center, National Cancer Institute, Rio de Janeiro, Brazil.
authors: David
authors: D
authors: Alfaro
authors: *Department of Cell Biology, Faculty of Biology, Complutense University of Madrid, Madrid, Spain; Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil; Pediatric Hematology and Oncology Program, Research Center, National Cancer Institute, Rio de Janeiro, Brazil.
authors: Javier
authors: J
authors: García-Ceca
authors: *Department of Cell Biology, Faculty of Biology, Complutense University of Madrid, Madrid, Spain; Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil; Pediatric Hematology and Oncology Program, Research Center, National Cancer Institute, Rio de Janeiro, Brazil.
authors: Desio A
authors: DA
authors: Farias-de-Oliveira
authors: *Department of Cell Biology, Faculty of Biology, Complutense University of Madrid, Madrid, Spain; Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil; Pediatric Hematology and Oncology Program, Research Center, National Cancer Institute, Rio de Janeiro, Brazil.
authors: Eugenia
authors: E
authors: Terra-Granado
authors: *Department of Cell Biology, Faculty of Biology, Complutense University of Madrid, Madrid, Spain; Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil; Pediatric Hematology and Oncology Program, Research Center, National Cancer Institute, Rio de Janeiro, Brazil.
authors: Sara
authors: S
authors: Montero-Herradón
authors: *Department of Cell Biology, Faculty of Biology, Complutense University of Madrid, Madrid, Spain; Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil; Pediatric Hematology and Oncology Program, Research Center, National Cancer Institute, Rio de Janeiro, Brazil.
authors: Vinicius
authors: V
authors: Cotta-de-Almeida
authors: *Department of Cell Biology, Faculty of Biology, Complutense University of Madrid, Madrid, Spain; Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil; Pediatric Hematology and Oncology Program, Research Center, National Cancer Institute, Rio de Janeiro, Brazil.
authors: Wilson
authors: W
authors: Savino
authors: *Department of Cell Biology, Faculty of Biology, Complutense University of Madrid, Madrid, Spain; Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil; Pediatric Hematology and Oncology Program, Research Center, National Cancer Institute, Rio de Janeiro, Brazil zapata@bio.ucm.es.
authors: Agustín
authors: A
authors: Zapata
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D054421:Chemokine CCL21 / Q000235:genetics / Q000276:immunology; D019742:Chemokines, CC / Q000235:genetics / Q000276:immunology; D036387:Ephrin-B1 / Q000235:genetics / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D036183:Receptor, EphB2 / Q000235:genetics / Q000276:immunology*; D036223:Receptor, EphB3 / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
chemical_list: C491541:Ccl25 protein, mouse; D054421:Chemokine CCL21; D019742:Chemokines, CC; C092571:Efnb1 protein, mouse; D036387:Ephrin-B1; C586311:Ephb2 protein, mouse; D036183:Receptor, EphB2; D036223:Receptor, EphB3
keywords: EphrinB; P-selectin; chemokines