Zhu J, Wang Y, Li J-X, et al. Donor Plasmacytoid Dendritic Cells Limit Graft-Versus-Host Disease Through Vasoactive Intestinal Polypeptide Expression. Blood. 2022; (doi: 10.1182/blood.2021012561).
Building on the discovery that plasmacytoid dendritic cells (pDCs) in bone marrow donor grafts limit the pathogenesis of graft-versus-host disease (GVHD), researchers identified Vasoactive Intestinal Peptide (VIP) expressed by those cells as the specific mechanism through which GVHD suppression is achieved. They report that VIP, an anti-inflammatory neuropeptide, converts hematopoietic stem cells into regulatory dendritic cells that inhibit GVHD in stem cell transplant recipients. VIP-expressing pDCs, in both mice and humans, limit T cell activation and expansion. In murine experiments, rodents were less likely to survive, more likely to have elevated GVHD scores, and more prone to colon crypt cell apoptosis if allogeneic bone marrow transplant (BMT) was conducted with VIP knockout pDCs than if it was executed with wild-type pDCs. BMT recipients of knockout pDCs exhibited more Th1 polarization, greater T cell expansion, and more pro-inflammatory cytokines than wild-type pDCs. The findings suggest a promising mechanism through which donor immune cells regulate T cell activation and GVHD in the setting of allogeneic BMT.