Using DMF to inhibit Tfh differentiation in the treatment of cGVHD
Lyu F, Gong H, Wu X, et al. Dimethyl Fumarate Ameliorates Chronic Graft-Versus-Host Disease by Inhibiting Tfh Differentiation via Nrf2. Leukemia. 2024; (doi: 10.1038/s41375-024-02475-5).
Researchers have learned that dimethyl fumarate (DMF), already known to suppress acute graft-versus-host disease (GVHD) without undermining graft-versus-leukemia effect, also has therapeutic promise against chronic GVHD (cGVHD). From observations in mice models, investigators determined that the anti-inflammatory medication works against cGVHD development by discouraging follicular helper T cell (Tfh) differentiation. It accomplishes this by activating Nrf2, which in turn leads to downregulation of IL-21 transcription. In different murine models, suppression of Tfh differentiation curbed the severity of disease. Tests using peripheral blood mononuclear cells from active cGVHD patients upheld the potential for treating post-allogeneic hematopoietic stem cell transplant patients with DMF, which reduced IL-21 production and Tfh cell generation.