The immune system provides an essential mechanism to protect our body from pathogens. However, the immune system requires strict control because its dysregulation directly causes various diseases. Moreover, chronic diseases, i.e., chronic infection and cancer, hijack and modify the immune system to promote their chronicity. Our laboratory is conducting basic and translational human immunology research aiming at achieving three goals: 1) To define the "norm" of immune responses in healthy subjects, 2) To define the "alterations" of the immune system in various diseases with a particular focus on the microenvironment, and 3) To elucidating the pathophysiology of the disease and developing new therapeutic strategies.
Immunology research with mouse models has contributed significantly to the increase of our knowledge of immunology. Nonetheless, it has become clear that there is a limitation in translating the findings in mice into humans. The differences between mice and humans in the cellular and molecular mechanisms of immune responses are widely recognized. The evolutionary divergence of mice and humans occurred about 96 million years ago. Mice and humans have different lifespans, living environments, and food. The history of infection and vaccination(!) as well as microflora are also vastly different. Therefore, it seems self-evident that there are many discrepancies between the findings obtained in mouse models and human clinical trials, likely due to differences in the uniquely evolved immune system. Therefore, human immunology research using human specimens is necessary to understand the human immune system.
In experiments with human samples, we often notice a wide range of heterogeneity in the immune responses. This is because the human immune system is significantly affected not only by the genome but also by many other environmental factors. Comparisons of the immune system between identical twins have demonstrated many differences in the immune system, including the immune cell composition in the blood, their ability to respond to external stimuli, and serum cytokine levels, proving that the immune system is primarily affected by environmental factors that do not depend on genetic information. Therefore, to elucidate the pathogenesis of diseases, it is crucial to define the common alterations in the immune system among the samples obtained from patients.
Research tools for human immunology research have dramatically evolved in the last 5-10 years with the progress of instruments and analytical methods. In-depth analysis at a single cell resolution has become possible even with a tiny piece of human tissue samples, such as inflamed tissues in autoimmune diseases and tumor tissues in cancer. This technological advancement has enabled us to gain direct insights into disease pathogenesis. We anticipate that the technological innovations for human immunology research will continue to accelerate, and the immunology research field will shift to human immunology.
In our laboratory, we will conduct advanced human immunology research using state-of-the-art methodology. By using various specimens obtained from healthy people and patients, we aim to achieve three goals: 1) To define the "norm" of immune responses in healthy subjects, 2) To define the "alterations" of the immune system in various diseases, with a particular focus on the tissue microenvironment, and 3) To elucidating the pathophysiology of the disease and developing new therapeutic strategies. Our target diseases are infectious diseases (including COVID-19), vaccines, cancer, autoimmune diseases, and allergies. In particular, we are interested in the immunology of the human liver.
Policy at the Ueno Lab
1
The basis:
Human specimens are essential for understanding human immunology.
2
Be cautious:
The findings in mouse models could, might, potentially be applied to humans. Or not.
3
With respect:
Human specimens should be treated with good faith and respect.
4
Appreciate heterogeneity:
Learn from each clinical sample/case.
5
Science in excellence:
Get as much information as you can with the latest technology.
6
Analyze!:
Data generation is useless without in-depth analysis.
Analysis of CD4+ T cell subsets specific for spike protein of SARS-CoV-2 in COVID-19 convalescent subjects by 5-laser Cytek Aurora FCM (left) and 10X Chromium 5’ scRNAseq (center). TCR clonal overlap in CD4+ T cell subsets between SARS-CoV-2- and Human common cold-coronaviruses- specific cells (right).Super-multicolor staining of an inflamed human liver tissue by using Fluidigm Hyperion.
