Fucoidan Can Function as an Adjuvant In Vivo to Enhance Dendritic Cell Maturation and Function and Promote Antigen-Specific T Cell Immune Responses

Jin, Jun‐O; Zhang, Wei; Du, Jiangyuan; Wong, Ka-Wing; Oda, Tatsuya; Yu, Qing

doi:10.1371/journal.pone.0099396

Cited by 124 publications

(122 citation statements)

References 34 publications

Supporting

Mentioning

110

Contrasting

Unclassified

Order By: Relevance

“…Notably, configurations where either IL-15:IL-15R␣ or OVA was detached from the NPs did not enhance animal sur- vival beyond the control group. Our findings align with recent literature showing that OVA vaccination requires an adjuvant to potentiate antigen-specific protective immunity (97)(98)(99)(100) and further highlight the importance of adjuvant configuration in the case of IL-15. Overall, we show that nanoparticles transpresenting IL-15:IL-15R␣ and encapsulating antigen demonstrate in vivo efficacy in the treatment of an aggressive model of murine melanoma.…”

Section: Il-15:il-15r␣ and Encapsulated Antigen Synergize To Delay Tusupporting

confidence: 91%

Configuration-dependent Presentation of Multivalent IL-15:IL-15Rα Enhances the Antigen-specific T Cell Response and Anti-tumor Immunity

Hong

Usiskin

Bergamaschi

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

It is well established that dendritic cells (DCs) 2 play a key role as professional antigen-presenting cells in initiating and coordinating antigen-specific adaptive immunity (1, 2). By constitutively sampling the external microenvironment through receptor-mediated and non-receptor mediated endocytic pathways, DCs initiate, program, and regulate the effector response against a variety of antigens (3-7). Although much is known about the immunobiology of DC antigen processing and presentation and the effect of different cytokines on DC maturation and their subsequent effect on the immune response (8), little is known about how the configuration or geometry of cytokine transmission affects the DC response. For example, physiologically, although IL-2 and IL-15 belong to the same four a-helix family of cytokines, IL-2 is transmitted as a soluble paracrine or autocrine factor (9, 10), whereas IL-15 is trans-presented on the surface of DCs and other cell types through a stable complex (11) with IL-15R␣ (12, 13) or secreted as a soluble paracrine complex (14, 15). The quality and manner by which cytokines are delivered to DCs can have a profound effect on the subsequent effector immune response (16,17).Nanosystems such as nanoparticles (18,19), nanotubes (20), or even macromolecular systems (21) comprise an emerging strategy for controlling antigen and cytokine transmission to . Perhaps one of the most explored carriers has been the polymeric poly(lactide-co-glycolide) (PLGA) system because of its significant promise and established effect in clinical settings (25-27) and well understood methods of formulation for delivery of small-molecule drugs, nucleic acids, and protein antigens (22, 28 -31). Several studies have demonstrated the promise of antigen-loaded PLGA nanoparticles as nanoparticle-based vaccines and delivery systems targeting DCs (32-39).IL-15 is a homeostatic cytokine for CD8 ϩ T cells and natural killer cells and an important regulator of the cytotoxic immune response (40). IL-15 signals by binding to cells expressing the IL-2/IL-15 ␤/␥ receptor and is found complexed to . This IL-15:IL-15R␣ complex is termed heterodimeric . IL-15R␣ is expressed by several cell types in * C. B. and G. N. P. are inventors on United States Government-owned patents and patent applications related to heterodimeric IL-15 and gene expression optimization. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

show abstract

Section: Il-15:il-15r␣ and Encapsulated Antigen Synergize To Delay Tusupporting

confidence: 91%

Configuration-dependent Presentation of Multivalent IL-15:IL-15Rα Enhances the Antigen-specific T Cell Response and Anti-tumor Immunity

Hong

Usiskin

Bergamaschi

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Various polysaccharides, including fucoidan, ascophyllan and λ-carrageenan, have shown immune activation and anti-cancer effects [3, 19, 23, 24]. In this study, we showed that pullulan, a polysaccharide purified from Aureobasidium pullulans , promoted the activation of BMDCs in vitro and of spleen DCs in vivo, and induced anti-cancer immune responses.…”

Section: Discussionmentioning

confidence: 66%

“…Different subsets of DCs have different abilities of Ag-presentation and T cell activation. In mouse, conventional DCs (cDC) have two subsets: CD8α + CD11c + and CD8α − CD11c + cDCs [3, 19, 20]. CD8α + CD11c + cDCs are specialized in the cross-presentation of endogenously synthesized Ags through MHC class I to CTL [20, 21], and CD8α − CD11c + cDCs have the selective ability to present extracellular Ags directly through MHC class II to CD4 T cells [22].…”

Section: Introductionmentioning

confidence: 99%

Maturation of dendritic cells by pullulan promotes anti-cancer effect

Zhang

Kwak

et al. 2016

Oncotarget

Self Cite

View full text Add to dashboard Cite

Previous studies have demonstrated that pullulan, a polysaccharide purified from Aureobasidium pullulans, has immune-stimulatory effects on T and B cells. Moreover, pullulan has been used as a carrier in the delivery of the antigen (Ag) peptide to lymphoid tissues. However, the in vivo effect of pullulan on dendritic cells (DC) has not been well characterized. In this study, we assessed the effect of pullulan on DC activation and anti-cancer immunity. The results showed that the pullulan treatment up-regulated co-stimulatory molecule expression and enhanced pro-inflammatory cytokine production in bone marrow-derived DCs (BMDC) in vitro and in spleen DCs in vivo. Moreover, the combination of ovalbumin (OVA) and pullulan induced OVA antigen-specific T cell activations in vivo. In tumor-bearing mice, pullulan induced the maturation of DCs in spleen and tumor draining lymph node (drLN), and promoted the OVA-specific T cell activation and migration of the T cells into the tumor. In addition, the combination of OVA and pullulan inhibited B16-OVA tumor growth and liver metastasis. The combination of tyrosinase-related protein 2 (TRP2) peptide and pullulan treatment also suppressed B16 melanoma growth. Thus, the results demonstrated that pullulan enhanced DC maturation and function, and it acted as an adjuvant in promoting Ag-specific immune responses in mice. Thus, pullulan could be a new and useful adjuvant for use in therapeutic cancer vaccines.

show abstract

“…Fucoidan , , , , , (Kuznetsova et al, 2014;Cho et al, 2015). , , , (Jin et al, 2014). fucoidan , , (Ahmed et al, 2014).…”

Section: 서 론 (Idiopathic Pulmonary Fibrosis Ipf)unclassified

Inhibitory Effect of Fucoidan on TGF-β1-Induced Activation of Human Pulmonary Fibroblasts

Yim¹,

Lee²,

Choi³

et al. 2016

Korean Journal of Fisheries and Aquatic Sciences

View full text Add to dashboard Cite

Fucoidan, one of the dominant sulfated polysaccharides extracted from brown seaweed, possesses a wide range of biological activities. Transforming growth factor-β (TGF-β) plays a pivotal role in the pathogenesis of pulmonary fibrosis, by stimulating the synthesis of profibrotic factors. In this study, we investigated the in vitro effects of fucoidan on collagen synthesis, α-smooth muscle actin (α-SMA) expression, and interleukin (IL)-6 production in TGF-β-stimulated human pulmonary fibroblasts. The expression of type I collagen and α-SMA was detected by Western blot, and the production of IL-6 by enzyme-linked immunosorbent assay. TGF-β1 treatment of pulmonary fibroblasts enhanced the expression of α-SMA, type I collagen, and IL-6 whereas these effects were inhibited in cells pretreated with fucoidan. The activation of Smad2/3, p38 mitogen-activated protein kinases (MAPKs), and Akt was also inhibited in fucoidan-pretreated, TGF-β1-stimulated human pulmonary fibroblasts. These data demonstrate the anti-fibrotic potential of fucoidan in TGF-β-induced human pulmonary fibroblasts, via the inhibition of Smad2/3, p38 MAPKs, and Akt phosphorylation. Our results suggest the therapeutic potential of fucoidan in the prevention or treatment of pulmonary fibrosis.

show abstract

Fucoidan Can Function as an Adjuvant In Vivo to Enhance Dendritic Cell Maturation and Function and Promote Antigen-Specific T Cell Immune Responses

Cited by 124 publications

References 34 publications

Configuration-dependent Presentation of Multivalent IL-15:IL-15Rα Enhances the Antigen-specific T Cell Response and Anti-tumor Immunity

Configuration-dependent Presentation of Multivalent IL-15:IL-15Rα Enhances the Antigen-specific T Cell Response and Anti-tumor Immunity

Maturation of dendritic cells by pullulan promotes anti-cancer effect

Inhibitory Effect of Fucoidan on TGF-β1-Induced Activation of Human Pulmonary Fibroblasts

Contact Info

Product

Resources

About