DCs populate almost all body surfaces and they do not kill the pathogens directly, they utilize and subsequently degrade antigens to peptides by their proteolytic activity.
[8][9][6] Tolerogenic DCs often display an immature or semi-mature phenotype with characteristically low expression of costimulatory (e.g. CD80, CD86) and MHC molecules on their surface.
[10][5] Tolerogenic DCs may be a potential candidate for specific immunotherapy and are studied for using them for treatment of inflammatory, autoimmune and allergic diseases and also in transplant medicine.
Important and interesting feature of tolerogenic DCs is also the migratory capacity toward secondary lymph organs, leading to T-cell mediated immunosuppression.
[13] Therefore, it is necessary to test tolerogenic DCs for a stable phenotype to exclude a loss of the regulatory function and a switch to an immunostimulatory activity.
[14][15][16][17] Tolerogenic effect has been demonstrated also by over-expression of Jagged-1 on DCs which in turn induced antigen specific T regulatory cells producing TGF-b.
It has been shown that following molecules induce/promote/favour induction of tol-DCs: IL-10, IL-27, TGF-b1, hepatocyte growth factor, vasoactive intestinal peptide, retinoid acid, vitamin D3, corticosteroids, rapamycin, cyclosporine, tacrolism, aspirin and ligands of AhR.
CD83high IL-10DCs display a stable phenotype under inflammatory conditions and show higher migratory capacity, providing migration to secondary lymphoid organs.
[5] In 2011, Giannoukakis et al. published results of randomized, double-blind phase I study of autologous DCs vaccination in type I diabetic patients.
[30][31][32] Tumours also developed ways of inducing tol-DCs resulting in differentiation and accumulation of Tregs in their stroma and draining lymph node.
[33][34] As already mentioned above many pharmacological substances are capable of inducing tol-DCs including corticosteroids, rapamycin, cyclosporine, tacrolism, aspirin,.
Genetic manipulations can used to confer tolerogenic properties on DCs such as gene knock down, knock-out, transgenic over expression of proteins and others.