Graphene quantum dots suppress proinflammatory T cell responses via autophagy-dependent induction of tolerogenic dendritic cells
Samo za registrovane korisnike
2017
Autori
Tomić, SergejJanjetović, Kristina D.
Mihajlovic, Dusan
Milenković, Marina
Kravić-Stevović, Tamara K.
Marković, Zoran M.
Todorović-Marković, Biljana
Špitalsky, Zdenko
Mičušik, Matej
Vucevic, Dragana
Colic, Miodrag
Trajković, Vladimir S.
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
Graphene quantum dots (GQD) are atom-thick nanodimensional carbon sheets with excellent physicochemical and biological properties; making them attractive for application in theranostics: However, their immunoregulatory properties are insufficiently investigated, especially in human primary immune cells. We found that non-toxic doses of GQD inhibit the production of proinflammatory and T helper (Th) 1 cytokines, and augment the production of anti-inflammatory and Th2 cytokines by human peripheral blood mononuclear cells. While unable to affect T cells directly, GQD impaired the differentiation and functions of monocyte-derived dendritic cells (DC), lowering their capacity to stimulate T cell proliferation, development of Thl and Th17 cells, and T-cell mediated cytotoxicity. Additionally, GQD-treated DC potentiated Th2 polarization, and induced suppressive CD4(+)CD25(high)Foxp3(+) regulatory T cells. After internalization in a dynamin-independent, cholesterol-dependent manner, GQD lowere...d the production of reactive oxygen species and nuclear translocation of NF-kappa B in DC. The activity of mammalian target of rapamycin (mTOR) was reduced by GQD, which correlated with the increase in transcription of autophagy genes and autophagic flux in DC. Genetic suppression of autophagy impaired the pro-tolerogenic effects of GQD on DC. Our results suggest that GQD-triggered autophagy promotes tolerogenic functions in monocyte-derived DC, which could be beneficial in inflammatory T-cell mediated pathologies, but also harmful in GQD-based anti-cancer therapy. (C) 2017 Elsevier Ltd. All rights reserved.
Ključne reči:
Graphene quantum dots / Dendritic cells / Tolerance / Regulatory T cells / AutophagyIzvor:
Biomaterials, 2017, 146, 13-28Finansiranje / projekti:
- Primena funkcionalizovanih ugljeničnih nanocevi i nanočestica zlata za pripremu dendritskih ćelija u terapiji tumora (RS-MESTD-Basic Research (BR or ON)-175102)
- Modulacija signalnih puteva koji kontrolišu intracelularni energetski balans u terapiji tumora i neuro-imuno-endokrinih poremećaja (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41025)
- Molekularna karakterizacija tumora štitaste žlezde: biološki i klinički aspekti (RS-MESTD-Basic Research (BR or ON)-173050)
- Medical Faculty of the Military Medical Academy [MF-VMA 08/13-15, MF-VMA 9/16-18]
DOI: 10.1016/j.biomaterials.2017.08.040
ISSN: 0142-9612; 1878-5905
PubMed: 28892752
WoS: 000412958000002
Scopus: 2-s2.0-85028917901
Kolekcije
Institucija/grupa
VinčaTY - JOUR AU - Tomić, Sergej AU - Janjetović, Kristina D. AU - Mihajlovic, Dusan AU - Milenković, Marina AU - Kravić-Stevović, Tamara K. AU - Marković, Zoran M. AU - Todorović-Marković, Biljana AU - Špitalsky, Zdenko AU - Mičušik, Matej AU - Vucevic, Dragana AU - Colic, Miodrag AU - Trajković, Vladimir S. PY - 2017 UR - https://vinar.vin.bg.ac.rs/handle/123456789/1782 AB - Graphene quantum dots (GQD) are atom-thick nanodimensional carbon sheets with excellent physicochemical and biological properties; making them attractive for application in theranostics: However, their immunoregulatory properties are insufficiently investigated, especially in human primary immune cells. We found that non-toxic doses of GQD inhibit the production of proinflammatory and T helper (Th) 1 cytokines, and augment the production of anti-inflammatory and Th2 cytokines by human peripheral blood mononuclear cells. While unable to affect T cells directly, GQD impaired the differentiation and functions of monocyte-derived dendritic cells (DC), lowering their capacity to stimulate T cell proliferation, development of Thl and Th17 cells, and T-cell mediated cytotoxicity. Additionally, GQD-treated DC potentiated Th2 polarization, and induced suppressive CD4(+)CD25(high)Foxp3(+) regulatory T cells. After internalization in a dynamin-independent, cholesterol-dependent manner, GQD lowered the production of reactive oxygen species and nuclear translocation of NF-kappa B in DC. The activity of mammalian target of rapamycin (mTOR) was reduced by GQD, which correlated with the increase in transcription of autophagy genes and autophagic flux in DC. Genetic suppression of autophagy impaired the pro-tolerogenic effects of GQD on DC. Our results suggest that GQD-triggered autophagy promotes tolerogenic functions in monocyte-derived DC, which could be beneficial in inflammatory T-cell mediated pathologies, but also harmful in GQD-based anti-cancer therapy. (C) 2017 Elsevier Ltd. All rights reserved. T2 - Biomaterials T1 - Graphene quantum dots suppress proinflammatory T cell responses via autophagy-dependent induction of tolerogenic dendritic cells VL - 146 SP - 13 EP - 28 DO - 10.1016/j.biomaterials.2017.08.040 ER -
@article{ author = "Tomić, Sergej and Janjetović, Kristina D. and Mihajlovic, Dusan and Milenković, Marina and Kravić-Stevović, Tamara K. and Marković, Zoran M. and Todorović-Marković, Biljana and Špitalsky, Zdenko and Mičušik, Matej and Vucevic, Dragana and Colic, Miodrag and Trajković, Vladimir S.", year = "2017", abstract = "Graphene quantum dots (GQD) are atom-thick nanodimensional carbon sheets with excellent physicochemical and biological properties; making them attractive for application in theranostics: However, their immunoregulatory properties are insufficiently investigated, especially in human primary immune cells. We found that non-toxic doses of GQD inhibit the production of proinflammatory and T helper (Th) 1 cytokines, and augment the production of anti-inflammatory and Th2 cytokines by human peripheral blood mononuclear cells. While unable to affect T cells directly, GQD impaired the differentiation and functions of monocyte-derived dendritic cells (DC), lowering their capacity to stimulate T cell proliferation, development of Thl and Th17 cells, and T-cell mediated cytotoxicity. Additionally, GQD-treated DC potentiated Th2 polarization, and induced suppressive CD4(+)CD25(high)Foxp3(+) regulatory T cells. After internalization in a dynamin-independent, cholesterol-dependent manner, GQD lowered the production of reactive oxygen species and nuclear translocation of NF-kappa B in DC. The activity of mammalian target of rapamycin (mTOR) was reduced by GQD, which correlated with the increase in transcription of autophagy genes and autophagic flux in DC. Genetic suppression of autophagy impaired the pro-tolerogenic effects of GQD on DC. Our results suggest that GQD-triggered autophagy promotes tolerogenic functions in monocyte-derived DC, which could be beneficial in inflammatory T-cell mediated pathologies, but also harmful in GQD-based anti-cancer therapy. (C) 2017 Elsevier Ltd. All rights reserved.", journal = "Biomaterials", title = "Graphene quantum dots suppress proinflammatory T cell responses via autophagy-dependent induction of tolerogenic dendritic cells", volume = "146", pages = "13-28", doi = "10.1016/j.biomaterials.2017.08.040" }
Tomić, S., Janjetović, K. D., Mihajlovic, D., Milenković, M., Kravić-Stevović, T. K., Marković, Z. M., Todorović-Marković, B., Špitalsky, Z., Mičušik, M., Vucevic, D., Colic, M.,& Trajković, V. S.. (2017). Graphene quantum dots suppress proinflammatory T cell responses via autophagy-dependent induction of tolerogenic dendritic cells. in Biomaterials, 146, 13-28. https://doi.org/10.1016/j.biomaterials.2017.08.040
Tomić S, Janjetović KD, Mihajlovic D, Milenković M, Kravić-Stevović TK, Marković ZM, Todorović-Marković B, Špitalsky Z, Mičušik M, Vucevic D, Colic M, Trajković VS. Graphene quantum dots suppress proinflammatory T cell responses via autophagy-dependent induction of tolerogenic dendritic cells. in Biomaterials. 2017;146:13-28. doi:10.1016/j.biomaterials.2017.08.040 .
Tomić, Sergej, Janjetović, Kristina D., Mihajlovic, Dusan, Milenković, Marina, Kravić-Stevović, Tamara K., Marković, Zoran M., Todorović-Marković, Biljana, Špitalsky, Zdenko, Mičušik, Matej, Vucevic, Dragana, Colic, Miodrag, Trajković, Vladimir S., "Graphene quantum dots suppress proinflammatory T cell responses via autophagy-dependent induction of tolerogenic dendritic cells" in Biomaterials, 146 (2017):13-28, https://doi.org/10.1016/j.biomaterials.2017.08.040 . .