RESUMEN
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.
Asunto(s)
Movimiento Celular/genética , Proteínas de la Membrana/genética , Proteínas del Tejido Nervioso/genética , Neuropilina-2/genética , Células Precursoras de Linfocitos T/metabolismo , Anticuerpos Bloqueadores/inmunología , Anticuerpos Bloqueadores/farmacología , Movimiento Celular/efectos de los fármacos , Células Cultivadas , Quimiocina CXCL12/farmacología , Niño , Preescolar , Expresión Génica , Humanos , Lactante , Recién Nacido , Lisofosfolípidos/farmacología , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/farmacología , Microscopía Confocal , Proteínas del Tejido Nervioso/metabolismo , Proteínas del Tejido Nervioso/farmacología , Neuropilina-2/inmunología , Neuropilina-2/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Esfingosina/análogos & derivados , Esfingosina/farmacología , Timocitos/metabolismo , Timo/citología , Timo/metabolismoRESUMEN
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.