Biology subjects

Mizukami, S.

Publications and source records attributed to Mizukami, S..

4 recordsLinked to original sources

bioRxiv2025

mRNA-Based Designer APCs Elicit Robust CD8⁺ and CD4⁺ T Cell Responses

mRNA-based therapeutics have demonstrated notable success in SARS-CoV-2 vaccines and are emerging in cancer immunotherapy. However, conventional mRNA cancer vaccines are limited by the low immunogenicity of tumor-associated and neoantigens. We addressed this limitation by formulating a modular, liposome-based mRNA cocktail comprising three distinct mRNAs encoding tumor antigen, the co-stimulatory molecule CD80, and membrane-tethered IL-2. Administration of this mRNA mixture transforms somatic cells into designer antigen-presenting cells (APCs) in vivo, which simultaneously express the antigen, a co-stimulatory molecule, and a cytokine. These designer APCs more effectively activated tumor antigen-specific CD8 T cells than mRNA encoding the antigen alone and elicited robust anti-tumor immune responses. In addition, substituting IL-2 in the mRNA mixtures with membrane-tethered IL-12 led to the expansion and differentiation of endogenous antigen-specific Th1 helper T cells in vivo. Importantly, this platform activated NY-ESO-1-specific CD8 T cells both in human PBMCs in vitro and in HLA-A*02:01-transgenic mice, highlighting its translational potential. This modular mRNA strategy reprograms somatic cells in situ into designer APCs, providing a flexible and translatable platform for precision immunotherapy.

immunology↗

bioRxiv2023

Zinc controls histone acetyltransferase KAT7 activity to maintain cellular zinc homeostasis

Zinc is an indispensable micronutrient for optimal physiological functions, and zinc deficiency has been implicated in the pathogenesis of various human diseases. One potential mechanism underlying such pathogenic effects is the alteration of gene expression caused by zinc deficiency; however, the details of this process remain largely unexplored. Here, we show that during zinc deficiency, the histone acetyltransferase KAT7 loses its enzymatic activity, leading to the attenuated acetylation of histone H3 at Lys14 (H3K14ac) at enhancer regions. Physiologically, the decrease in H3K14ac leads to the upregulation of the expression of ZIP10, a plasma membrane-localized zinc transporter, thereby facilitating the import of extracellular zinc to maintain cellular zinc homeostasis. Moreover, prolonged zinc deficiency in mice induced by a zinc-deficient diet or high-fat diet, accompanied by decreased H3K14ac levels in the liver, upregulated the expression of genes associated with intracellular lipid droplet formation, leading to the accumulation of lipids within liver tissue. Our findings demonstrate that cells respond to zinc deficiency by converting it into an epigenetic signal that drives physiological or pathophysiological biological processes.

cell biology↗

bioRxiv2020

Single-cell dynamics of pannexin-1-facilitated programmed ATP loss during apoptosis

ATP is essential for all living cells. However, how dead cells lose ATP has not been well investigated. In this study, we developed new FRET biosensors for dual imaging of intracellular ATP level and caspase-3 activity in single apoptotic cultured human cells. We show that the cytosolic ATP level starts to decrease immediately after the activation of caspase-3, and this process is completed typically within 2 hours. The ATP decrease was facilitated by caspase-dependent cleavage of the plasma membrane channel pannexin-1, indicating that the intracellular decrease of the apoptotic cell is a "programmed" process. Apoptotic cells deficient of pannexin-1 sustained the ability to produce ATP through glycolysis and to consume ATP, and did not stop wasting glucose much longer period than normal apoptotic cells. Thus, the pannexin-1 plays a role in arresting the metabolic activity of dead apoptotic cells, most likely through facilitating the loss of intracellular ATP. (148 words)

cell biology↗

bioRxiv2019

Knowledge of Chagas disease in Latin American migrant population living in Japan and factors associated with knowledge level

BackgroundChagas disease (CD), typically confined to the Latin America (LA) region, is emerging as a global health problem. In Japan, as in the rest of world, the under-diagnose rate of CD is alarmingly high. Various studies have highlighted the importance of informed knowledge in the seeking behavior. Educational integrative activities, with consideration for socio-cultural factors, can help increase the knowledge of the participants. There has been no studies that analyze the difference in knowledge, before and after these educational activities. This study aimed to qualitatively and quantitatively investigate the knowledge, behavior and attitude toward CD among LA migrants in Japan and to evaluate the effectiveness of the community educational activity in increasing knowledge of CD.\n\nMethodologyThis cross-sectional study involved two questionnaires to analyze the knowledge of the LA migrant participants before and after the community activity (CA) in four cities in Japan (Oizumi, Suzuka, Hadano, and Nagoya).\n\nPrincipal FindingsA total of 75 participants were enrolled, predominantly Bolivians from hyperendemic areas. The baseline knowledge of CD was low. However, most of them were familiar with the disease although less than 10% of them had been tested for CD before. Living in Japan for more than 10 years and previously being tested for CD were the factors associated with better knowledge. The conducted CA significantly improved the knowledge of the participants. They associated the term \"Chagas\" mostly with fear and concern. In contrast to other studies, the level of stigmatization was low. The barriers in care seeking behavior were language, migration process and difficulties to access to the healthcare system.\n\nConclusionEducational activities with integrative approach are useful to increase knowledge of CD. The activity brings the possibility to explore not only the level of knowledge, but also to reveal the experience and to understand the needs of the people at risk.\n\nAuthor SummaryThough the incident rate of Chagas disease (CD) has fallen, more than 7 million people are affected worldwide. The CD prevalence is under-estimated because just 1% of these affected people can access to the diagnosis and treatment. This situation is maintaining mainly for the lack of implication of socio-cultural factors in the interventions to decrease the burden of the disease. Educational activities with integral approach are useful to increase the knowledge of the people at risk. People that have being tested for CD before or living in Japan for more than 10 years have better knowledge about the disease, suggesting the importance of knowledge in the seeking behavior. The authors recommend the implementation of educational activities with integral approach as a strategy to improves the knowledge of Chagas disease among Latin America migrants in Japan.

scientific communication and education↗