Fundamental Study for Treatment of Important Disorders using Integrative Control Function of Immune Systems/CRDS-FY2006-SP-02
Executive Summary

Abnormal or excessive immune responses are deeply involved in the causes and incidence of immune diseases. Although the control of such immune responses is the global challenge, the clinical application is not easy.

This proposal aims to establish a novel and highly versatile foundation for medical care based on the following research achievements that have been promoted mainly by researchers in Japan and rapidly growing in recent years:

[1] Elucidation of a mechanism of immunological tolerance by regulatory T cells that comprehensively inhibit and control the immune system,
[2] Integrated understanding of natural immunity and acquired immunity and the utilization based on rapid progress in the recognition of infecting parasites by natural immune system and the study on defense against infection
[3] Elucidation of molecular mechanism of immunological phenomena and comprehensive understanding and utilization of building of higher-order immune tissues and formation of immunological organs both of which are indispensable for the application

Immunological control is the result of general reaction of an individual organism. The quality and quantity (degree) are regulated by the total of cellular proliferation, differentiation and maturation of cells responsible for various kinds of immunity which are gathered in the “place of immune reaction” (hereinafter referred to as “place”). Therefore, an effective clinical application is impossible unless there is the understanding of place along with the elucidation of elementary steps on a molecular and cellular level. This strategic program aims to understand these issues comprehensively and overcome the following issues that are deeply linked with each other.

(1) Development of a stable therapeutic method by artificially controlling immune reaction in the development and maintenance of pathological conditions of intractable autoimmune diseases (rheumatoid arthritis, autoimmune diabetes, etc.) and allergic diseases such as hay fever, atopic dermatitis and asthma, establishment of preventive immunological control method and reduction of incidence of such diseases.
(2) Overcoming the difficulty of cancer immunity induction and cancellation of decline in immune reaction in tumor-bearing condition. Elucidation of various barriers that inevitably come with introduction of advanced medical technologies for cancer treatment, etc. (radiation injury, drug adverse reaction, etc.) and development of a method to overcome them.
(3) Development and establishment of a new immunological control technology that overcomes rejection associated with organ transplant and organ regenerative medicine in a self-regulating manner.
(4) Establishment of a strategy to develop new-generation vaccines (edible vaccines, inhaled vaccines) based on integrated understanding of natural immunity and acquired immunity by targeting mucosal tissues that are responsible for the primary control against emerging/re-emerging infections including respiratory and alimentary infections such as influenza and diarrhea, as well as bioterrorism that abuse the principle.

Although the research on the above issues is expected to be promoted and expanded mainly at universities, if it is designed by three players, that is, research institutes including RIKEN which promotes intensive research for each specialized theme, hospitals and universities, with a network of supplementing each one’s features and fostering successors, we can expect Japan’s leading role in the development of advanced medical care.