Creating innovative science for resolution of inflammation: Resilience and entropy of inflamed tissue. -Grant-in-Aid for Transformative Research Areas(B)



Purpose of the Research Project

Creating innovative science for resolution of inflammation:
resilience and entropy of inflamed tissue.

Tissues, which are damaged by various causes, including infection with harmful pathogens or ischemic injury, demonstrate the “tissue resilience function” to resume their normal state to maintain organ homeostasis. Resolution of inflammation is characterized as self-limiting processes: clearance of the infiltrated inflammatory cells and restoration of damaged tissues. Meanwhile, ex-inflamed tissues store “inflammatory memories”, diverse biological information derived from the inflammation, and particularly, the accumulation of “pathological inflammatory memories”. The deposition of inflammation-generated factors, which we termed “tissue damage entropy”, leads to flare-ups or prolongation of inflammation as well as irreversible remodeling and subsequent tissue dysfunction. The next generation of therapies for intractable diseases will need to focus on how to restore better functioning tissues by means of successful elimination of “inflammatory memories” and correction of “tissue damage entropy”. To achieve this purpose, an integrated understanding of the mechanisms of tissue resilience, especially during the resolution of inflammation, is required; however, it is difficult to grasp the whole picture of the machinery of tissue resilience because various biological systems, such as the immune system and the nervous system, are interconnected in a multilayered fashion.

In this research area, we will elucidate the biological responses of physiological tissue resilience and inflammatory memory during the resolution of inflammation. Furthermore, we will revisit the pathogenesis of chronic inflammation from our distinctive perspective such as inflammatory tissue resilience, pathological inflammatory memory and tissue damage entropy, through which we aim to create a new discipline related to the resolution of inflammation.