title: Cathepsin E Deficiency Ameliorates Graft-versus-Host Disease and Modifies Dendritic Cell Motility.
abstract: Microbial products influence immunity after allogeneic hematopoietic stem cell transplantation (allo-SCT). In this context, the role of cathepsin E (Ctse), an aspartate protease known to cleave bacterial peptides for antigen presentation in dendritic cells (DCs), has not been studied. During experimental acute graft-versus-host disease (GVHD), we found infiltration by Ctse-positive immune cells leading to higher Ctse RNA- and protein levels in target organs. In Ctse-deficient allo-SCT recipients, we found ameliorated GVHD, improved survival, and lower numbers of tissue-infiltrating DCs. Donor T cell proliferation was not different in Ctse-deficient vs. wild-type allo-SCT recipients in MHC-matched and MHC-mismatched models. Furthermore, Ctse-deficient DCs had an intact ability to induce allogeneic T cell proliferation, suggesting that its role in antigen presentation may not be the main mechanism how Ctse impacts GVHD. We found that Ctse deficiency significantly decreases DC motilityin vivo, reduces adhesion to extracellular matrix (ECM), and diminishes invasion through ECM. We conclude that Ctse has a previously unrecognized role in regulating DC motility that possibly contributes to reduced DC counts and ameliorated inflammation in GVHD target organs of Ctse-deficient allo-SCT recipients. However, our data do not provide definite proof that the observed effect of Ctse-/-deficiency is exclusively mediated by DCs. A contribution of Ctse-/--mediated functions in other recipient cell types, e.g., macrophages, cannot be excluded.
authors.affiliation: Medical Department, Division of Hematology, Oncology and Tumor Immunology, Charité University Medicine , Berlin , Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Mengwasser
authors.affiliation: Faculty of Medicine, BIOSS Centre for Biological Signalling Studies, Institute of Molecular Medicine and Cell Research, Albert-Ludwigs-University Freiburg , Freiburg , Germany.
authors.forename: Liane
authors.initials: L
authors.lastname: Babes
authors.affiliation: Medical Department, Division of Hematology, Oncology and Tumor Immunology, Charité University Medicine , Berlin , Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Cordes
authors.affiliation: Medical Department, Division of Hematology, Oncology and Tumor Immunology, Charité University Medicine , Berlin , Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Mertlitz
authors.affiliation: Medical Department, Division of Hematology, Oncology and Tumor Immunology, Charité University Medicine , Berlin , Germany.
authors.forename: Katarina
authors.initials: K
authors.lastname: Riesner
authors.affiliation: Medical Department, Division of Hematology, Oncology and Tumor Immunology, Charité University Medicine , Berlin , Germany.
authors.forename: Yu
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Medical Department, Division of Hematology, Oncology and Tumor Immunology, Charité University Medicine , Berlin , Germany.
authors.forename: Aleixandria
authors.initials: A
authors.lastname: McGearey
authors.affiliation: Medical Department, Division of Hematology, Oncology and Tumor Immunology, Charité University Medicine , Berlin , Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Kalupa
authors.affiliation: Faculty of Medicine, BIOSS Centre for Biological Signalling Studies, Institute of Molecular Medicine and Cell Research, Albert-Ludwigs-University Freiburg , Freiburg , Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Reinheckel
authors.affiliation: Medical Department, Division of Hematology, Oncology and Tumor Immunology, Charité University Medicine , Berlin , Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Penack
keywords: GVHD; HSCT; cathepsin E; dendritic cells; motility