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 + CD25 high 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. Keywords: Dendritic cells r Mesenchymal stem cells r Periapical lesions r Th polarizationAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionPeriapical lesions (PLs) are a common pathology within the human population initiated by the bacterial invasion of the root canal and develop from an acute inflammatory response to the formation of granulomas or cysts infiltrated by various inflammatory cells [1].Correspondence: Prof. MiodragČolić e-mail: fakultet.vma@mod.gov.rs Furthermore, cytokines produced by Th cells have been shown to play a crucial role in PLs pathogenesis. Namely, Th1-and Th17-derived cytokines promote inflammation, bone resorption, and disease progression. Th2 cells seem to be important for the later phases of PLs development, whereas IL-10 and TGF-β produced by Treg cells seem to be important for the healing processes within PLs [2,3]. However, it is not yet clear which mediators and cells are involved crucially in the regulation of Th-cell commitment during the development, maintenance, and resolution of the disease.C 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2013. 43: 1862-1872 Immunomodulation 1863DCs are the key regulatory and decision-making cells with a unique ability to activate naive T cells and polarize their development. These cells can be differentiated in vitro from monocytes or CD34 + -progenitors with GM-CSF and IL-4, generating CD1a + CD14 − immature DCs (iDCs) [4]. Alternatively, in the absence of IL-4, GM-CSF induces the differ...

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In this paper, facile synthesis of water soluble curcumin nanocrystals is reported. Solvent exchange method was applied to synthesize curcumin nanocrystals. Different techniques were used to characterize the structural and photophysical properties of curcumin nanocrystals. We found that nanocurcumin prepared by this method had good chemical and physical stability, could be stored in the powder form at room temperature, and was freely dispersible in water. It was established that the size of curcumin nanocrystals was varied in the range of 20-500 nm. Fourier transform infrared spectroscopy and UV-Vis analyses showed the presence of tetrahydrofuran inside the curcumin nanocrystals. Also, it was found that nanocurcumin emitted photoluminescencewith yellow-green colour. [Projekat Ministarstva nauke Republike Srbije, br. 172003]

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