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CONTROL OF HUMAN THYMOCYTE MIGRATION BY NEUROPILIN-1/SEMAPHORIN-3A-MEDIATED INTERACTIONS
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Université René Descartes Paris V. Centre National de la Recherche Scientifique Unité Mixte de Recherche 8147. Paris, France. Paris, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ. Brasil / Universidade Federal de Alagoas. Departamento de Morfologia. Maceió, AL, Brasil.
Université Paris V René Descartes. Institut National de la Santé et de la Recherche Médicale Unité 648. Paris, France / TRAGEX Pharma. Tour Reflets. 75015 Paris, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ. Brasil.
Université René Descartes Paris V. Centre National de la Recherche Scientifique Unité Mixte de Recherche 8147. Paris, France. Paris, France.
Université René Descartes Paris V. Centre National de la Recherche Scientifique Unité Mixte de Recherche 8147. Paris, France. Paris, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ. Brasil /
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ. Brasil / Universidade Federal de Alagoas. Departamento de Morfologia. Maceió, AL, Brasil.
Université Paris V René Descartes. Institut National de la Santé et de la Recherche Médicale Unité 648. Paris, France / TRAGEX Pharma. Tour Reflets. 75015 Paris, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ. Brasil.
Université René Descartes Paris V. Centre National de la Recherche Scientifique Unité Mixte de Recherche 8147. Paris, France. Paris, France.
Université René Descartes Paris V. Centre National de la Recherche Scientifique Unité Mixte de Recherche 8147. Paris, France. Paris, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Imunologia. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ. Brasil /
Abstract
It is largely established that molecules first discovered in the nervous system are also found in the immune system. Neuropilin-1 (NP-1) was initially identified to mediate semaphorin-induced chemorepulsion during brain development and is also involved in peripheral T cell/dendritic cell interactions. Herein, we studied NP-1 during T cell development in the human thymus. NP-1 is expressed in both cortex and medulla of thymic lobules, being found in distinct CD4/CD8-defined thymocyte subsets. NP-1 is also found in thymic epithelial cells (TEC) in situ and in vitro, and is recruited at the site of TEC–thymocyte contact. Moreover, NP-1 was rapidly
up-regulated during thymocyte stimulation by T cell receptor (TCR) and IL-7 or after adhesion to TEC. Semaphorin-3A (Sema-3A), a natural ligand of NP-1, is also present in human thymus, both in TEC and thymocytes, being up-regulated in thymocytes after TCR engagement. Functionally, Sema-3A decreases the adhesion capacity of NP-1 thymocytes and induces their migration by a repulsive effect. In conclusion, we show here that NP-1/Sema-3A-mediated interactions participate in the control of human thymocyte development.
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