June 9, 2023
Keio University School of Medicine
A research group led by Associate Professor Nobuhiro Nakamoto and Professor Takanori Kanai of the Division of Gastroenterology and Hepatology, Keio University School of Medicine, along with collaborative researcher Sodai Fujimori of Mitsubishi Tanabe Pharma Corporation, has for the first time revealed that B cells exacerbate autoimmune hepatitis (AIH) by promoting the proliferation of cytotoxic CD8+ T cells through the secretion of IL-15, a type of cytokine.
AIH is a form of hepatitis designated as an intractable disease in Japan, caused by an abnormality in the immune system where the body's own immune cells attack the liver. It has been previously reported that drugs that deplete B cells are effective in some patients with refractory AIH. While elucidating the mechanism by which B cells worsen the disease could lead to the development of new treatments, this mechanism is extremely complex and has been difficult to unravel.
In this study, using a mouse model of AIH where B cell involvement is confirmed, the research group conducted a comprehensive analysis of gene expression in B cells within the model. This led to the first-time discovery that the secretion of IL-15 is a key function. IL-15 has the effect of promoting the proliferation of cytotoxic CD8+ T cells, which are important immune cells that damage the liver. While these cells are abundant in the spleen, the study newly demonstrated a series of pathogenic mechanisms: B cells promote the proliferation of CD8+ T cells in the spleen, which then migrate to the liver and exacerbate hepatitis. Furthermore, it was also revealed that CD8+ T cells stimulate B cells to induce IL-15 expression, indicating a reciprocal interaction. These research findings are expected to contribute to the development of treatment strategies and new drugs for AIH.
These research findings were published in JHEP Reports on April 6, 2023 (JST).
For the full press release, please see below.