Adams RC, Carter-Cusack D, Shaikh SN, et al. Donor Bone Marrow-Derived Macrophage MHC II Drives Neuroinflammation and Altered Behavior During Chronic GVHD in Mice. Blood. 2021; (doi: 10.1182/blood.2021011671).
Researchers now understand that mediators of chronic graft-versus-host disease (cGVHD) presenting in the central nervous system differ from those observed in acute GVHD, with expression of donor bone marrow-derived macrophages (BMDM) MHC class II strongly implicated in the former. In particular, cGVHD is characterized by behavioral impairments linked to broad neuroinflammation and persistent lfng upregulation. In acute GVHD, resident microglia-derived tumor necrosis factor has recently been shown to mediate neuroinflammation in the cortex of mice and humans. Scientists noted the immunological differences between the two types of disease through preclinical murine models of cGVHD. The divergent mechanisms influencing each underscore the need for scientists to explore alternative treatment targets for neurological manifestations once the disease reaches the late stage.