December 12, 2023
Keio University School of Medicine
A research group led by Associate Professor Shunsuke Takaba and Professor Akihiko Yoshimura of the Department of Microbiology and Immunology, Keio University School of Medicine, used a mouse model of autoimmune dermatitis to analyze the properties and in vivo dynamics of pathogenic T cells involved in treatment resistance and recurrence of autoimmune diseases.
Using experiments to track skin-attacking pathogenic T cells in vivo, they revealed that there are two groups of pathogenic T cells: inflammatory T cells, which are completely suppressed by the immunosuppressant abatacept, and memory-like T cells, which are not suppressed and remain latent in the body. Inflammatory T cells were regenerated from the memory-like T cells that did not respond to the immunosuppressant, suggesting that this is involved in relapse after discontinuation of the immunosuppressant. Furthermore, a detailed analysis of the memory-like T cells revealed that these cells highly express the aldehyde dehydrogenase (ALDH) gene. It was found that administering cyanamide (an ALDH inhibitor), an alcohol-aversion drug used as an adjunct in alcoholism treatment, to mice could inhibit the survival of latent memory-like cells in vivo.
This study has revealed part of the mechanism by which cells causing autoimmune diseases resist immunosuppressants and "stubbornly" survive in the body. This suggests the potential for immunotherapy targeting these cells.
The results of this research were published in the American scientific journal iScience on December 8, 2023.
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