Laboratory of Developmental Programming
and Immuno-Physiology
Origin of heterogeneity in immunity
Inter-individual heterogeneity in immune response is well recognized. Studies with twins found that environmental factors play more dominant role over genetic factors in the establishment of immune cell composition and function. Particularly, various early-life environment has been recognized to affect long-term immune cell composition and function. We are interested in the mechanism of long-term immune programming by various perinatal environmental factors.
Immuno-Physiology
Upon exposure to various environmental factors, physiological responses are initiated, which are largely mediated by various endocrine hormones and metabolites. These factors promote proper energy and resource allocation to activate appropriate body program for the adaptation. Immune responses are also regulated with the same signals. We pursue the integrative understanding of the rationale in this interaction between immune responses and physiological changes. We adopt 'life history theory' as our theoretical basis to understand this interaction. Furthermore, we ask whether long-term immune programming is possible with the early modulation of these physiological factors.
Developmental Plasticity
To understand the long-term programming by early-life environmental factors, we adopted the idea of developmental plasticity as a theoretical basis for our study. Developmental plasticity is a process of adaptation reported in various species. In this process, environmental factors directly affect the development of phenotypes that is suitable for the adaptation to predicted environment. Due to the irreversible nature of expressed phenotype, it can have long-term consequences. We pursue the understanding of the rationale and mechanism of long-term programming of phenotype by early environmental exposure.
Developmental programming of immunity by perinatal host-microbiota interaction
Persistent immune modulation with specific perinatal environmental exposure is well recognized in the field of allergy and asthma, as proposed in hygiene hypothesis. Now the cases of long-term immune programming by specific perinatal microbiota exposure are accumulating. However, the framework for this phenomenon is still elusive. We suggest that perinatal host and microbiota interaction shapes each other for the long-term establishment of commensals and tissue resident immune cells, thereby leading to heterogeneity of later-life immune response.
Metastable Epialleles
Ultimate goal of our research is to identify developmental mechanism of long-term maintenance of a phenotype established with early-life environment. One of our particular interests is 'metastable epialleles'. These epialleles is the loci in the genome that can have different epigenomic state upon environmental exposure during development. For example, one carbon metabolism during development affects DNA methylation of Agouti loci in mice, leading to dramatic phenotypic difference. Understanding the mechanism of this epigenetic programming may lead to discovery of fundamental biological rules in developmental programming.
Role of Immuno-Physiology on Cancer initiation, progression and metastasis
Recent success of cancer immunotherapy clearly demonstrates the importance of immune system for anti-tumor immunity. Immune system can also support tumor growth by inducing tumor-promoting inflammation and /or by establishing tolerogenic microenvironment. In spite of these progresses, fundamental biological aspects behind the immuno-oncology are still largely unexplored. We will study the environmental input on immuno-oncology. Particularly, we will focus on endocrine and metabolic regulation of immunity and its consequence on tumor development.
