The TLR7 ligand R848 prevents mouse graft-versus-host disease and cooperates with anti-interleukin-27 antibody for maximal protection and regulatory T-cell upregulation.

ABSTRACT: In spite of considerable therapeutic progress, acute graft-versus-host disease still limits allogeneic hematopoietic cell transplantation. We recently reported that mouse infection with nidovirus lactate dehydrogenase elevating virus impairs disease in non-conditioned B6D2F1 recipients of parental B6 spleen cells. As this virus activates TLR7, we tested a pharmacological TLR7 ligand, R848, in this model and observed complete survival if donor and recipients were treated before transplantation. Mixed lymphocyte culture performed 48 h after R848-treatment of normal mice demonstrated that both T-cell allo-responsiveness and antigen presentation by CD11b⁺ and CD8α⁺ dendritic cells were inhibited. These inhibitions were dependent on IFNAR-1 signaling. In the B6 to B

SUBMITTER: Gaignage M 

PROVIDER: S-EPMC6355498 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature