Immunosuppressive nanoparticles containing recombinant PD-L1 and methotrexate alleviate multi-organ inflammation.

Multi-organ inflammatory diseases are one of the most serious autoimmune diseases worldwide. The regulation of immune responses by immune checkpoint proteins influences the development and treatment of cancer and autoimmune diseases. In this study, recombinant murine PD-L1 (rmPD-L1) was used for controlling T cell immunity to treat multi-organ inflammation. To enhance the immunosuppressive effect, we incorporated methotrexate, an anti-inflammatory drug, into hybrid nanoparticles (HNPs) and decorated the surface of HNPs with rmPD-L1 to produce immunosuppressive HNPs (IsHNPs). IsHNP treatment effectively targeted PD-1-expressing CD4 and CD8 T cells in the splenocytes; additionally, it promoted the production of Foxp3-expressing regulatory T cells, which suppressed the differentiation of helper T cells. IsHNP treatment also inhibited anti-CD3 antibody-mediated activation of CD4 and CD8 T cells in mice in vivo. This treatment protected mice from multi-organ inflammation induced by the adoptive transfer of naïve T cells to recombination-activating gene 1 knockout mice. The results of this study imply the therapeutic potential of IsHNPs in the treatment of multi-organ inflammation and other inflammatory diseases.

Pyropia yezoensis-derived porphyran attenuates acute and chronic colitis by suppressing dendritic cells.

Porphyran is known to inhibit immune cell function. Previously, porphyran was shown to prevent lipopolysaccharide-induced sepsis in mice. However, studies on the inhibitory effects of porphyran during colitis are currently lacking. In this study, we evaluated the effects of Pyropia yezoensis-derived porphyran on dextran sodium sulfate (DSS)-induced acute and chronic colitis. The oral or intraperitoneal administration of porphyran inhibited the progression of DSS-induced colitis in mice, with the former also preventing immune cell infiltration in the colon. The levels of intracellular interferon-γ and interleukin-17 in T cells decreased when porphyran was administered orally. Porphyran inhibited T cell activation by suppressing dendritic cells (DCs) and macrophages. Porphyran prevented pathogen-associated molecular pattern and damage-associated molecular pattern-dependent DC and macrophage activation. Finally, porphyran attenuated chronic colitis caused via the long-term administration of DSS. These findings indicate that the oral administration of porphyran can inhibit DSS-induced colitis by suppressing DC and macrophage activation.

Ecklonia cava fucoidan has potential to stimulate natural killer cells in vivo.

Fucoidan is a sulfated polysaccharide, derived from various marine brown seaweeds, that has immunomodulatory effects. In this study, we analyzed the effects of five different fucoidans, which were extracted from Ascophyllum nodosum, Undaria pinnatifida, Macrocystis pyrifera, Fucus vesiculosus, and Ecklonia cava, on natural killer (NK) cell activation in mice. Among these, E. cava fucoidan (ECF) promoted an increase in the number of NK cells in the spleen and had the strongest effect on the activation of NK cells. Additionally, we observed that DC stimulation was required for NK cell activation and that ECF had the most potent effect on splenic dendritic cells (DC). Finally, ECF treatment effectively prevented infiltration of CT-26 carcinoma cells in the lungs of BALB/c mice in an NK cell dependent manner. Collectively, these results suggest that ECF could be a suitable candidate for enhancing NK cell-mediated anti-cancer immunity.

Comparison of human peripheral blood dendritic cell activation by four fucoidans.

Brown seaweed is an important source of fucoidan, which displays immunomodulatory effects by activating various immune cells. However, these effects of fucoidans from various sources of brown seaweed have not yet been explored in human blood dendritic cells. We studied fucoidans extracted from Ecklonia cava, Macrocystis pyrifera, Undaria pinnatifida, and Fucus vesiculosus for their effects on human monocyte-derived dendritic cells (MODC) and human peripheral blood DC (PBDC) activation. Ecklonia cava fucoidan (ECF) strongly upregulated co-stimulatory molecules, major histocompatibility complex class I and II, and the production of proinflammatory cytokines in MODCs and PBDCs compared to those by the other three fucoidans. Moreover, ECF elicited the strongest effect in the induction of syngeneic T cell proliferation and IFN-γ production compared to those of other fucoidans. These results suggest that ECF could be a suitable candidate molecule for enhancing immune activation in humans compared to that with the other three fucoidans.