Role of retinoic acid and vitamin D in the activation and migration of CD3/CD28/CD46 activated CD4+ T cells

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• Título: Role of retinoic acid and vitamin D in the activation and migration of CD3/CD28/CD46 activated CD4+ T cells
• Autor: Camargo Latorre, Daniel Santiago
• Publicación original: 2014
• Descripción física: PDF
• Nota general:
  • T cells play a central role in the inflammation occurring in multiple sclerosis (MS) and migration of activated T cells into the central nervous system (CNS) is key to MS pathogenesis. The production of inflammatory mediators and leukocyte chemotaxis into the central nervous system are essential in the inflammation observed in patients with MS. It is known that vitamin D modulates the CD46 pathway in T cells, while retinoic acid forces mast cells to augment cytokine’s expression and thus trigger a pro-inflammatory profile. This project consisted in investigating the migratory potential of CD46-activated T cells and to compare this to the activation pathway engaged by the costimulatory molecule CD28, within the context of multiple sclerosis, and what controls the expression of chemokine receptors and adhesion molecules in the inflammatory response. We assessed the expression of CD46, CD69, CD25, OX40. CD11A, VLA4, CD29, CXCR3 and CCR7 in CD3, CD28 and CD46 activated CD4+ T cells treated with RA or VD by FACS.
    The effect of MnCl2 over beta 2 integrin activation was studied under RA/VD-treated T cells. Chemotaxis of CD28/CD46-activated T cells was analysed in transwell plates and assessed by FACS. Moreover, we used HUVEC within the transwell system to assess the effect of integrin binding to its ligand as well as the interaction between chemokine receptors and chemokines. We found that CD3 and CD3/CD28-activated T cells increased the expression of all the activation markers (CD46, CD69, CD25 and OX40), integrins and CXCR3 but didn’t change the expression of the chemokine receptor CCR7. Meanwhile, CD3/CD46-activated T cells increased the expression of the same molecules except for CD46 and CCR7. We show here that RA increased the expression of CD69, OX40, VLA4 and CD29 but decreased the expression of CD11A and didn’t have an effect over CD46, CD25, CXCR3 and CCR7. VD increased the expression of CD69 and CD29, but decreased the expression of CD11A and VLA4, and had no effect on CD46, CD25, OX40, CXCR3 and CCR7.
    We probed MnCl2 as a promoter of activation of the beta 2 integrin (LFA-1). The activation of beta 2 integrin was higher in CD3/CD28 and CD3/CD46-activated CD4+ T cells than in CD3-activated cells. Thus CD28 and CD46 activation increases the migratory profile of T cells. RA and VD have no effect in the role of MnCl2 in the activation of beta 2 integrin. Our results suggest that after 3 hours incubation, RA prompts chemotaxis in CD46-activated cells which are related to a decrease in CD46 expression and thus a pro-migratory profile, while VD stimulates chemotaxis in CD28-activated cells that have a high CD46 expression related to a regulation of T-cell induced inflammatory events. Meanwhile, after the overnight incubation both RA and VD promote a more regulatory phenotype due to higher CD46 expression. The chemotaxis assays with HUVEC should be optimized. These results indicate that retinoic acid promotes a pro-migratory and pro-inflammatory profile, while vitamin D acts as a regulator of T cell recruitment and proliferation, thus reducing the risk of developing MS.
• Notas de reproducción original: Digitalización realizada por la Biblioteca Virtual del Banco de la República (Colombia)
• Notas:
  • Resumen: Multiple sclerosis; T cells; Nervous system; CD46; Cells
  • © Derechos reservados del autor
  • Colfuturo
• Forma/género: tesis
• Idioma: inglés
• Institución origen: Biblioteca Virtual del Banco de la República
• Encabezamiento de materia:
  • Ciencias naturales y matemáticas; Ciencias naturales y matemáticas / Ciencias de la vida Biología