ICOSL⁺ plasmacytoid dendritic cells as inducer of graft-versus-host disease, responsive to a dual ICOS/CD28 antagonist.

ABSTRACT: Acute graft-versus-host disease (aGVHD) remains a major complication of allogeneic hematopoietic cell transplantation (HCT). CD146 and CCR5 are proteins that mark activated T helper 17 (Th17) cells. The Th17 cell phenotype is promoted by the interaction of the receptor ICOS on T cells with ICOS ligand (ICOSL) on dendritic cells (DCs). We performed multiparametric flow cytometry in a cohort of 156 HCT recipients and conducted experiments with aGVHD murine models to understand the role of ICOSL⁺ DCs. We observed an increased frequency of ICOSL⁺ plasmacytoid DCs, correlating with CD146⁺CCR5⁺ T cell frequencies, in the 64 HCT recipients with gastrointestinal aGVHD. In murine models, donor bone marrow cells from ICOSL-deficient mice compared to those

SUBMITTER: Adom D 

PROVIDER: S-EPMC7811191 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature