Control of human thymocyte migration by Neuropilin-1/Semaphorin-3A-mediated interactions.
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.
Lepelletier
Yves
Y
Centre National de la Recherche Scientifique Unité Mixte de Recherche 8147, Université René Descartes Paris V, Hôpital Necker, 75743 Paris, France.
Smaniotto
Salete
S
Hadj-Slimane
Réda
R
Villa-Verde
Déa Maria Serra
DM
Nogueira
Ana Cristina
AC
Dardenne
Mireille
M
Hermine
Olivier
O
Savino
Wilson
W
D002448:Cell Adhesion; D002465:Cell Movement; D002633:Chemotaxis; D005109:Extracellular Matrix / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D016023:Integrins / Q000378:metabolism; D015851:Interleukin-7 / Q000378:metabolism; D008024:Ligands; D039942:Neuropilin-1 / Q000378:metabolism*; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D040121:Semaphorin-3A / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism; D015854:Up-Regulation
D016023:Integrins; D015851:Interleukin-7; D008024:Ligands; D011948:Receptors, Antigen, T-Cell; D040121:Semaphorin-3A; D039942:Neuropilin-1