- Modulation of immune tolerance: the role of tolerogenic dendritic cells and TNFα
S.M. van Ham
J.A. ten Brinke
- Award date
- 26 October 2012
- Number of pages
- Document type
- PhD thesis
- Faculty of Science (FNWI)
- Swammerdam Institute for Life Sciences (SILS)
This thesis describes the role of tolerogenic DC and anti-TNFÎ± 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-TNFÎ± 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 IFNÎ³ production. Anti-TNFÎ± 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 TNFÎ± 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-TNFÎ± agents synergistically enhance immune suppression. Combination therapy of tDC and anti-TNFÎ± agents may therefore improve tolerance induction therapy in patients with TNFÎ±-mediated inflammatory diseases such as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, multiple sclerosis and inflammatory bowel diseases.
- Research conducted at: Universiteit van Amsterdam
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