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Ephitelial cells control dendritic cell function and regulatory T cell homeostasis in the gut : supervisor: M. Rescigno ; added co-supervisor: U. Cavallaro ; University of Milano, Faculty of medicine

Iliev, Iliyan Dimitrov <1977- >

Tesi o dissertazioni - 2009

Dendritic cells (DCs) isolated from the gut have been shown to display specialized functions, including the ability to promote gut tropism to B and T lymphocytes, to polarize non-inflammatory responses and to drive the differentiation of adaptive Foxp3+ T regulatory (Treg) cells. However, very little is known on what drives the mucosal phenotype of DCs. In this thesis we present evidence that both in human and mouse the local microenvironment, and in particular intestinal epithelial cells (IECs), promote the differentiation of tolerogenic DCs able to drive the development of adaptive Foxp3+ Treg cells. EC-derived TGF-b and retinoic acid (RA), and in humans also Thymic-stromal lymphopoietin (TSLP), are required for DC conversion. Accordingly, functionally altered human ECs derived from Crohn’s disease patients, have reduced ability to induce tolerogenic DC with Treg polarizing capacity. A subpopulation of gut CD103+ DCs is known to induce the expression of gut homing receptors on T cells and to drive Treg cell development in mice [...]
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