Fucoidan, a sulfated polysaccharide purified from brown algae, has a variety of immune-modulation effects, such as promoting activation of dendritic cells (DCs), natural killer (NK) cells and T cells, and enhancing anti-viral and anti-tumor responses. However, the immune-modulatory effect of fucoidan from different seaweed extracts has not been thoroughly analyzed and compared. We analyzed fucoidans obtained from Ascophyllum nodosum (A. nodosum), Macrocystis pyrifera (M. pyrifera), Undaria pinnatifida (U. pinnatifida) and Fucus vesiculosus (F. vesiculosus) for their effect on the apoptosis of human neutrophils, activation of mouse NK cells, maturation of spleen DCs, proliferation and activation of T cells, and the adjuvant effect in vivo. Fucoidans from M. pyrifera and U. pinnatifida strongly delayed human neutrophil apoptosis at low concentration, whereas fucoidans from A. nodosum and F. vesiculosus delayed human neutrophil apoptosis at higher concentration. Moreover, fucoidan from M. pyrifera promoted NK cell activation and cytotoxic activity against YAC-1 cells. In addition, M. pyrifera fucoidan induced the strongest activation of spleen DCs and T cells and ovalbumin (OVA) specific immune responses compared to other fucoidans. These data suggest that fucoidan from M. pyrifera can be potentially useful as a therapeutic agent for infectious diseases, cancer and an effective adjuvant for vaccine.

Multifunctional core-shell nanostructures formed by integration of distinct components have received wide attention as promising biological platforms in recent years. In this work, crystalline zeolitic imidazolate framework-8 (ZIF-8), a typical metal-organic framework (MOF), is coated onto single gold nanorod (AuNR) core for successful realization of synergistic photothermal and chemotherapy triggered by near-infrared (NIR) light. Impressively, high doxorubicin hydrochloride (DOX) loading capacity followed by pH and NIR light dual stimuli-responsive DOX release can be easily implemented through formation and breakage of coordination bonds in the system. Moreover, under NIR laser irradiation at 808 nm, these novel AuNR@MOF core-shell nanostructures exhibit effective synergistic chemo-photothermal therapy both in vitro and in vivo, confirmed by cell treatment and tumor ablation via intravenous injection.

The development of Ag-presenting functions by murine dendritic cells (DCs) of the CD8+ DC lineage was studied using a Flt-3 ligand stimulated bone-marrow culture system. Although newly formed DCs of this lineage are capable of Ag uptake and efficient presentation to T cells on MHC class II, they initially lack the ability to cross-present exogenous Ags on MHC class I. Cross-presentation capacity is acquired as a subsequent maturation step, promoted by cytokines such as GM-CSF. The development of cross-presentation capacity by the DCs in these cultures may be monitored by the parallel development of DC surface expression of CD103. However, the expression of CD103 and cross-presentation capacity are not always linked; therefore, CD103 is not an essential part of the cross-presentation machinery. These results explain the considerable variability in CD103 expression by CD8+ DCs as well as the findings that not all DCs of this lineage are capable of cross-presentation.

Fucoidan, a sulfated polysaccharide purified from brown algae, has a variety of immune-modulation effects, including promoting antigen uptake and enhancing anti-viral and anti-tumor effects. However, the effect of fucoidan in vivo, especially its adjuvant effect on in vivo anti-tumor immune responses, was not fully investigated. In this study, we investigated the effect of fucoidan on the function of spleen dendritic cells (DCs) and its adjuvant effect in vivo. Systemic administration of fucoidan induced up-regulation of CD40, CD80 and CD86 expression and production of IL-6, IL-12 and TNF-α in spleen cDCs. Fucoidan also promoted the generation of IFN-γ-producing Th1 and Tc1 cells in an IL-12-dependent manner. When used as an adjuvant in vivo with ovalbumin (OVA) antigen, fucoidan promoted OVA-specific antibody production and primed IFN-γ production in OVA-specific T cells. Moreover, fucoidan enhanced OVA-induced up-regulation of MHC class I and II on spleen cDCs and strongly prompted the proliferation of OVA-specific CD4 and CD8 T cells. Finally, OVA immunization with fucoidan as adjuvant protected mice from the challenge with B16-OVA tumor cells. Taken together, these results suggest that fucoidan can function as an adjuvant to induce Th1 immune response and CTL activation, which may be useful in tumor vaccine development.

Compared with its pro-inflammatory function, the mechanisms underlying the anti-inflammatory effect of IL-6 are poorly understood. IL-6 can cooperate with TGF-β to induce IL-10 production in Th17 cells in vitro. However, the effect of IL-6 on generation of Tr1 cells and the in vivo importance of this effect are mostly uncharacterized. In this study, we showed that in vitro, IL-6 can induce the generation of IL-10-producing Tr1 cells from naïve CD4 T cells, independently of IL-27 and TGF-β. IL-6 induces IL-21 production in CD4 T cells and IL-10-inducing effect of IL-6 requires both IL-21 and IL-2. Although IL-6 cannot induce IL-10 production in CD8 T cells in a cell-autonomous manner, it can do so indirectly through promoting CD4 T cell IL-21 production. The IL-10-producing T cells induced by IL-6 have phenotypic, genetic and functional traits of Tr1 cells and can suppress LPS-induced in vivo inflammatory response in an IL-10-dependent fashion. Blockade of IL-6 in two autoimmune inflammation models, induced respectively by anti-CD3 antibody or Treg-depletion, led to reduction in IL-10-producing T cells and exacerbated inflammation of lung and intestine. Thus, we delineated critical pathways involved in IL-6-induced generation of Tr1 cells and demonstrated the importance of this event in restraining autoimmune tissue inflammation.