Zoekopdracht:
faculteit: "FNWI" en publicatiejaar: "2012"
| Auteur | M.A. Boks | | Titel | Modulation of immune tolerance: the role of tolerogenic dendritic cells and TNFα |
| Promotor | S.M. van Ham |
| Co-promotors | J.A. ten Brinke, J.J. Zwaginga |
| Datum | 26-10-2012 |
| Jaar | 2012 |
| Pagina's | 149 |
| ISBN | 978-94-6182-153-9 |
| Faculteit | Faculteit der Natuurwetenschappen, Wiskunde en Informatica |
| Instituut/afd. | FNWI: Swammerdam Institute for Life Sciences (SILS) |
| Samenvatting | This thesis describes the role of tolerogenic DC and anti-TNFα agents in tolerance induction. IL-10-generated tDC potently induce Treg, while inhibiting CD4+ T cell proliferation and cytokine production by Th1 and Th2 cell subsets. Anti-TNFα shares this dual function; inducing IL-10 production and a regulatory phenotype and function in naïve CD4+ T cells, and at the same time counteracting CD4+ effector T cell priming by inhibiting activation status, survival and IFNγ production. Anti-TNFα upregulates inhibitory molecules galectin-3, legumain, GARP and LAG-3 which may be involved in (cell contact-dependent) suppressive function, as is described for natural Treg. In addition, chemokine and chemokine receptor expression are altered after TNFα neutralization, suggesting a change in chemoattraction by Treg and chemotaxis of Treg, thereby regulating the encounter with other immune cells. The picture emerges that tDC and anti-TNFα agents synergistically enhance immune suppression. Combination therapy of tDC and anti-TNFα agents may therefore improve tolerance induction therapy in patients with TNFα-mediated inflammatory diseases such as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, multiple sclerosis and inflammatory bowel diseases. |
| Taal | English |
| Soort document | Proefschrift |
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