immunostimulatory-agent-evaluation-lymphoid-tissue-extraction

Immunostimulatory Agent Evaluation: Lymphoid Tissue Extraction and Injection Route-Dependent Dendritic Cell Activation

For evaluation of a new therapeutic agent for immunotherapy or vaccination, analysis of immune cell activation in lymphatic tissues is essential. Here, we ...

Asan Medical Center

The Uba6-Use1 ubiquitin enzyme cascade is a poorly understood arm of the ubiquitin-proteasome system required for mouse development. Recently, we reported that Uba6 brain-specific knockout (termed NKO) mice display abnormal social behavior and neuronal development due to a decreased spine density and accumulation of Ube3a and Shank3. To better characterize a potential role for NKO mice in autism spectrum disorders (ASDs), we performed a comprehensive behavioral characterization of the social behavior and communication of NKO mice. Our behavioral results confirmed that NKO mice display social impairments, as indicated by fewer vocalizations and decreased social interaction. We conclude that UBA6 NKO mice represent a novel ASD mouse model of anti-social and less verbal behavioral symptoms. 

Impairment of social behavior and communication in mice lacking the Uba6-dependent ubiquitin activation system.

Lipopolysaccharide (LPS) is a well-known stimuli of dendritic cells (DCs). However, in vivo spleen DC maturation by Escherichia coli (E.coli) LPS has not been fully investigated. In this study, we examined the effect of LPS on the activation of spleen DCs and its subsets in a time-dependent manner on mice in vivo. The frequency, number and migration of spleen conventional DCs (cDCs) were increased 6 and 12h after completion of LPS treatment. Those increased DC numbers in spleen were then gradually decreased with apoptosis of the DCs. The highest levels of co-stimulatory molecule expression in the spleen cDCs and their subsets occurred 18h after LPS treatment, while the pro-inflammatory cytokines reached their maximum in the intracellular levels of the spleen cDCs and their subsets 3h after LPS treatment. The antigen presentation of the spleen cDCs and their subsets increased gradually from 3 to 12h after LPS treatment, but those levels decreased rapidly after 18h post-LPS treatment. Thus, by highlighting the importance of time in the stimulation of spleen DCs by LPS in mice in vivo, our data provided a model that could be used by immunologists when considering the manipulation of DC functions in vivo for experimental and clinical applications.

Time-dependent effect of E. coli LPS in spleen DC activation in vivo: Alteration of numbers, expression of co-stimulatory molecules, production of pro-inflammatory cytokines, and presentation of antigens.

The UBA6-specific E2 conjugating enzyme 1 (USE1) ubiquitin enzyme cascade is a poorly characterized arm of the ubiquitin-proteasome system. We investigated whether the UBA6-USE1 enzyme cascade plays a role in lung cancer tumorigenesis.

Association of Uba6-Specific-E2 (USE1) With Lung Tumorigenesis.

In our previous study, we showed that Rehmannia glutinosa polysaccharide (RGP) treatment induced maturation of dendritic cells (DCs) and that it had an anticancer effect in mice. The effect of RGP has not been studied in human DCs, including monocyte-derived DCs (MDDCs) and peripheral blood DCs (PBDCs). In this study, we examined DC activation by RGP in human cells. The dendritic morphology of RGP-treated MDDCs was substantially altered as compared with that of phosphate-buffered saline (PBS)-treated control cells. Moreover, RGP treatment markedly decreased phagocytic activity and increased expression levels of co-stimulatory molecules in MDDCs. In addition, RGP treatment elevated the production of proinflammatory cytokines. Furthermore, RGP-induced activation of MDDCs was dependent on the phosphorylation of extracellular signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK). RGP-treated MDDCs promoted upregulation of T-cell activation, including proliferation and interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) production. Analysis of the effect of RGP in PBDC subsets revealed that it induced upregulation of co-stimulatory molecule expression and proinflammatory cytokine production. These data suggest that RGP may function as an immune stimulatory molecule in humans.

Article	Year
Impairment of social behavior and communication in mice lacking the Uba6-dependent ubiquitin activation system. Behavioural brain research\| PubMed ID: 25523030	2015
Time-dependent effect of E. coli LPS in spleen DC activation in vivo: Alteration of numbers, expression of co-stimulatory molecules, production of pro-inflammatory cytokines, and presentatio... Molecular immunology\| PubMed ID: 28285188	2017
Association of Uba6-Specific-E2 (USE1) With Lung Tumorigenesis. Journal of the National Cancer Institute\| PubMed ID: 28376205	2017
Rehmannia glutinosa polysaccharide promoted activation of human dendritic cells. International journal of biological macromolecules\| PubMed ID: 29715554	2018

Peter C.W. Lee

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