EphB2-mediated interactions are essential for proper migration of T cell progenitors during fetal thymus colonization (original) (raw)

Journal Article

,

Department of Cell Biology, Faculties of Biology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation

, Rio de Janeiro,

Brazil

Department of Cell Biology, Faculties of Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation

, Rio de Janeiro,

Brazil

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Department of Cell Biology, Faculties of Medicine, Complutense University

, Madrid, Spain, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro,

Brazil

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,

Department of Cell Biology, Faculties of Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation

, Rio de Janeiro,

Brazil

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,

Department of Cell Biology, Faculties of Biology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation

, Rio de Janeiro,

Brazil

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,

Department of Cell Biology, Faculties of Biology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation

, Rio de Janeiro,

Brazil

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,

Department of Cell Biology, Faculties of Biology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation

, Rio de Janeiro,

Brazil

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,

Department of Cell Biology, Faculties of Biology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation

, Rio de Janeiro,

Brazil

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,

Department of Cell Biology, Faculties of Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation

, Rio de Janeiro,

Brazil

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Department of Cell Biology, Faculties of Biology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation

, Rio de Janeiro,

Brazil

Correspondence: Department of Cell Biology, Faculty of Biology, Complutense University, C/José Antonio Nováis, sn, 28040 Madrid, Spain. E-mail: zapata@bio.ucm.es

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Received:

10 February 2010

Revision received:

26 April 2010

Cite

Marco A Stimamiglio, Eva Jiménez, Suse D Silva-Barbosa, David Alfaro, José J García-Ceca, Juan J Muñoz, Teresa Cejalvo, Wilson Savino, Agustín Zapata, EphB2-mediated interactions are essential for proper migration of T cell progenitors during fetal thymus colonization, Journal of Leukocyte Biology, Volume 88, Issue 3, September 2010, Pages 483–494, https://doi.org/10.1189/jlb.0210079
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Abstract

Recruitment of lymphoid progenitors to the thymus is compromised by the lack of Eph/ephrin signaling in both T-cell progenitors and thymic microenvironmental cells

The ephrin-Eph ligand receptor pair is known to control the repulsion/adhesion process in different tissues, including the immune system. Herein, we evaluated the role of EphB2 receptors in T cell progenitor migration during in vitro thymus colonization and to ECM or chemokine stimuli. EphB2 and their ligands, ephrin-B1 and ephrin-B2, are expressed in BM-derived progenitors, and EphB2−/− cells had diminished thymus colonization capacity. Conversely, EphB2LacZ cells, which maintain a preserved ephrin-binding domain, were capable of colonizing WT thymuses similarly to WT progenitors, highlighting the importance of reverse signals transmitted to normal fetal thymus. However, the EphB2 receptor expressed by microenvironmental cells also drives progenitor immigration, as recolonization of EphB2-deficient fetal thymuses was compromised profoundly. Additionally, we observed lower depositions of ECM and chemokines on EphB2-deficient thymuses but no changes in their receptor expression on BM-derived progenitors and developing thymocytes. Migration of EphB2-deficient progenitors and thymocytes was also reduced through ECM or chemokine stimuli. Furthermore, ephrin-B1 costimulation also inhibited haptotaxis and chemotaxis of WT but not EphB2LacZ cells, demonstrating the specific involvement of EphB2 signaling on T cell progenitor migration. Our data suggest the relevance of a nonactivated EphB2 for regulating T cell progenitor migration and its modulation upon ephrin-B engagement.

© 2010 Society for Leukocyte Biology

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