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- Title
Mesenchymal stem cells from periapical lesions modulate differentiation and functional properties of monocyte-derived dendritic cells.
- Authors
Đokić, Jelena; Tomić, Sergej; Marković, Milan; Milosavljević, Petar; Čolić, Miodrag
- Abstract
Immunoregulatory mechanisms within periapical lesions ( PLs) are as of yet unexplored. Considering the crucial role of DCs in controlling the immune response within PLs, the immunomodulatory properties of mesenchymal stem cells ( MSCs), and the colocalization of MSCs and DCs in situ, we wondered whether MSCs from PLs modulate the development and functions of DCs. Using a model of monocyte-derived DCs, we showed that PL-MSCs inhibited differentiation of DCs via soluble factors, of which IL-6 had a minor effect, but did not impair their subsequent maturation induced by pro-inflammatory cytokines. However, upon maturation such DCs favored the production of Th2/ Th17 cytokines by allogenic CD4+ lymphocytes in coculture, compared with mature DCs differentiated without PL-MSCs. PL-MSC-differentiated DCs, cultivated with pro-inflammatory cytokines and PL-MSCs, although phenotypically mature, exhibited poor allostimulatory activity, induced anergy, Th2 polarization, differentiation of suppressive CD4+ CD25high CD39+ Treg-cell subsets via IDO-1-, ILT-3-, and ILT-4-dependent mechanisms, and increased production of TGF-β in the coculture. In contrast, DCs cultivated with PL-MSCs only during maturation stimulated proliferation and Th1 polarization of CD4+ T cells in an IL-12-independent manner. In conclusion, PL-MSCs significantly modulate the development and functions of DCs, depending on the phase of DCs development during which the interaction occurs.
- Publication
European Journal of Immunology, 2013, Vol 43, Issue 7, p1862
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.201243010