title: Native cellulose nanofibrills induce immune tolerance in vitro by acting on dendritic cells.
abstract: Cellulose nanofibrills (CNFs) are attractive biocompatible, natural nanomaterials for wide biomedical applications. However, the immunological mechanisms of CNFs have been poorly investigated. Considering that dendritic cells (DCs) are the key immune regulatory cells in response to nanomaterials, our aim was to investigate the immunological mechanisms of CNFs in a model of DC-mediated immune response. We found that non-toxic concentrations of CNFs impaired the differentiation, and subsequent maturation of human monocyte-derived (mo)-DCs. In a co-culture with CD4(+)T cells, CNF-treated mo-DCs possessed a weaker allostimulatory and T helper (Th)1 and Th17 polarizing capacity, but a stronger capacity to induce Th2 cells and CD4(+)CD25(hi)FoxP3(hi) regulatory T cells. This correlated with an increased immunoglobulin-like transcript-4 and indolamine dioxygenase-1 expression by CNF-treated mo-DCs, following the partial internalization of CNFs and the accumulation of CD209 and actin bundles at the place of contacts with CNFs. Cumulatively, we showed that CNFs are able to induce an active immune tolerance by inducing tolerogenic DCs, which could be beneficial for the application of CNFs in wound healing and chronic inflammation therapies.
authors: University of Defense, Medical Faculty of the Military Medical Academy, Institute for Medical Research, Belgrade, Serbia.
authors: Sergej
authors: S
authors: Tomić
authors: University of Maribor, Faculty of Mechanical Engineering, Institute for Engineering Materials and Design, Maribor, Slovenia.
authors: Vanja
authors: V
authors: Kokol
authors: University of Defense, Medical Faculty of the Military Medical Academy, Institute for Medical Research, Belgrade, Serbia.
authors: Dušan
authors: D
authors: Mihajlović
authors: University of Belgrade, Institute of Histology and Embryology, School of Medicine, Belgrade, Serbia.
authors: Aleksandar
authors: A
authors: Mirčić
authors: University of Defense, Medical Faculty of the Military Medical Academy, Institute for Medical Research, Belgrade, Serbia.|University of Belgrade, Institute for Application of Nuclear Energy, Belgrade, Serbia.
authors: Miodrag
authors: M
authors: Čolić
mesh_terms: D002454:Cell Differentiation; D016764:Cell Polarity; D002478:Cells, Cultured; D002482:Cellulose / Q000276:immunology* / Q000378:metabolism; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007378:Interleukins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D057139:Nanofibers; D058504:Th17 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D007378:Interleukins; D008070:Lipopolysaccharides; D002482:Cellulose