Semaphorin 3F and neuropilin-2 control the migration of human T-cell precursors

Daniella Arêas Mendes-da-Cruz; Anne Colette Brignier; Vahid Asnafi; Frederic Baleydier; Carolina Valença Messias; Yves Lepelletier; Nawel Bedjaoui; Amedée Renand; Salete Smaniotto; Danielle Canioni; Pierre Milpied; Karl Balabanian; Philippe Bousso; Stéphane Leprêtre; Yves Bertrand; Hervé Dombret; Norbert Ifrah; Mireille Dardenne; Elizabeth Macintyre; Wilson Savino; Olivier Hermine

doi:10.1371/journal.pone.0103405

Semaphorin 3F and neuropilin-2 control the migration of human T-cell precursors

PLoS One. 2014 Jul 28;9(7):e103405. doi: 10.1371/journal.pone.0103405. eCollection 2014.

Authors

Daniella Arêas Mendes-da-Cruz¹, Anne Colette Brignier², Vahid Asnafi³, Frederic Baleydier³, Carolina Valença Messias⁴, Yves Lepelletier⁵, Nawel Bedjaoui³, Amedée Renand⁶, Salete Smaniotto⁷, Danielle Canioni⁸, Pierre Milpied⁶, Karl Balabanian⁹, Philippe Bousso¹⁰, Stéphane Leprêtre¹¹, Yves Bertrand¹², Hervé Dombret¹³, Norbert Ifrah¹⁴, Mireille Dardenne⁶, Elizabeth Macintyre³, Wilson Savino⁴, Olivier Hermine¹⁵

Affiliations

¹ CNRS UMR8147, Paris Descartes University, Paris, France; Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
² CNRS UMR8147, Paris Descartes University, Paris, France; Department of Clinical Hematology, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
³ Laboratory of Oncohematology, AP-HP, Necker Children's Hospital, INSERM U1151, Paris, France.
⁴ Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
⁵ CNRS UMR8147, Paris Descartes University, Paris, France; INSERM U1163, CNRS ERL 8254, Laboratory of cellular and molecular basis of hematological disorders and their therapeutic implications, Imagine Institute, Paris, France.
⁶ CNRS UMR8147, Paris Descartes University, Paris, France.
⁷ Department of Morphology, Federal University of Alagoas, Maceió, Brazil.
⁸ Laboratory of Oncohematology, AP-HP, Necker Children's Hospital, INSERM U1151, Paris, France; Department of Morphology, Federal University of Alagoas, Maceió, Brazil.
⁹ INSERM U819 - Pasteur Institute, Paris, France.
¹⁰ INSERM U668 - Pasteur Institute, Paris, France.
¹¹ Department of Hematology, Centre Henri Becquerel, Rouen, France.
¹² Service of Pediatric Hematology, Hôpital Debrousse, Lyon, France.
¹³ University Paris 7, Hôpital Saint-Louis, AP-HP, and Institut Universitaire d'Hématologie EA3518, Paris, France.
¹⁴ Pôle de Recherche et d'Enseignement Supérieur l'Université Nantes Angers Le Mans, Centre Hospitalier Universitaire Angers, Service des Maladies du Sang and INSERM U892, Angers, France.
¹⁵ CNRS UMR8147, Paris Descartes University, Paris, France; Laboratory of Oncohematology, AP-HP, Necker Children's Hospital, INSERM U1151, Paris, France; INSERM U1163, CNRS ERL 8254, Laboratory of cellular and molecular basis of hematological disorders and their therapeutic implications, Imagine Institute, Paris, France.

Abstract

Neuropilins and semaphorins are known as modulators of axon guidance, angiogenesis, and organogenesis in the developing nervous system, but have been recently evidenced as also playing a role in the immune system. Here we describe the expression and role of semaphorin 3F (SEMA3F) and its receptor neuropilin-2 (NRP2) in human T cell precursors. NRP2 and SEMA3F are expressed in the human thymus, in both lymphoid and non-lymphoid compartments. SEMA3F have a repulsive effect on thymocyte migration and inhibited CXCL12- and sphingosine-1-phosphate (S1P)-induced thymocyte migration by inhibiting cytoskeleton reorganization prior to stimuli. Moreover, NRP2 and SEMA3F are expressed in human T-cell acute lymphoblastic leukemia/lymphoma primary cells. In these tumor cells, SEMA3F also blocks their migration induced by CXCL12 and S1P. Our data show that SEMA3F and NRP2 are further regulators of human thymocyte migration in physiological and pathological conditions.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Blocking / immunology
Antibodies, Blocking / pharmacology
Cell Movement / drug effects
Cell Movement / genetics*
Cells, Cultured
Chemokine CXCL12 / pharmacology
Child
Child, Preschool
Gene Expression
Humans
Infant
Infant, Newborn
Lysophospholipids / pharmacology
Membrane Proteins / genetics*
Membrane Proteins / metabolism
Membrane Proteins / pharmacology
Microscopy, Confocal
Nerve Tissue Proteins / genetics*
Nerve Tissue Proteins / metabolism
Nerve Tissue Proteins / pharmacology
Neuropilin-2 / genetics*
Neuropilin-2 / immunology
Neuropilin-2 / metabolism
Precursor Cells, T-Lymphoid / metabolism*
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Sphingosine / analogs & derivatives
Sphingosine / pharmacology
Thymocytes / metabolism
Thymus Gland / cytology
Thymus Gland / metabolism

Substances

Antibodies, Blocking
Chemokine CXCL12
Lysophospholipids
Membrane Proteins
Nerve Tissue Proteins
Neuropilin-2
SEMA3F protein, human
neuropilin-2, human
sphingosine 1-phosphate
Sphingosine

Grants and funding

This work was developed in the context of the CNRS-Fiocruz Associated Laboratory of Immunology and Immunopathology. It was partially funded with grants by CNRS/Fiocruz French/Brazilian conjoint program, CNRS, The Foundation for Medical Research (FRM - France), The National League against the Cancer (France), The National Cancer Institute (France); Fiocruz, CNPq, Faperj and CAPES (Brazil); Fund for Structural Convergence of Mercosur (FOCEM/Mercosur). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.