B lymphocytes protect islet ? cells in diabetes prone NOD mice treated with imatinib.

ABSTRACT: Imatinib (Gleevec) reverses type 1 diabetes (T1D) in NOD mice and is currently in clinical trials in individuals with recent-onset disease. While research has demonstrated that imatinib protects islet ? cells from the harmful effects of ER stress, the role the immune system plays in its reversal of T1D has been less well understood, and specific cellular immune targets have not been identified. In this study, we demonstrate that B lymphocytes, an immune subset that normally drives diabetes pathology, are unexpectedly required for reversal of hyperglycemia in NOD mice treated with imatinib. In the presence of B lymphocytes, reversal was linked to an increase in serum insulin concentration, but not an increase in islet ? cell mass or proliferation. However, improved ? cell function was reflected by a partial recovery of MafA transcription factor expression, a sensitive marker of islet ? cell stress that is important to adult ? cell function. Imatinib treatment was found to increase the antioxidant capacity of B lymphocytes, improving reactive oxygen species (ROS) handling in NOD islets. This study reveals a novel mechanism through which imatinib enables B lymphocytes to orchestrate functional recovery of T1D ? cells.

SUBMITTER: Wilson CS 

PROVIDER: S-EPMC6538336 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature