RESUMO
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.
Assuntos
Movimento Celular/genética , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Neuropilina-2/genética , Células Precursoras de Linfócitos T/metabolismo , Anticorpos Bloqueadores/imunologia , Anticorpos Bloqueadores/farmacologia , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Quimiocina CXCL12/farmacologia , Criança , Pré-Escolar , Expressão Gênica , Humanos , Lactente , Recém-Nascido , Lisofosfolipídeos/farmacologia , Proteínas de Membrana/metabolismo , Proteínas de Membrana/farmacologia , Microscopia Confocal , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/farmacologia , Neuropilina-2/imunologia , Neuropilina-2/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Esfingosina/análogos & derivados , Esfingosina/farmacologia , Timócitos/metabolismo , Timo/citologia , Timo/metabolismoRESUMO
Some molecules described in the nervous system are also expressed in cells involved in the control of the immune response, suggesting they have a role as common mechanisms between neuroendocrine and immune systems. In this review, we focus on the expression and role of neuropilins (NPs) and their soluble ligands class 3 semaphorins in thymus physiology, particularly migration of developing thymocytes. We also discuss the concept of multivectorial thymocyte migration, including semaphorins, as a new individual cell migration vector.