Cathepsin E Deficiency Ameliorates Graft-versus-Host Disease and Modifies Dendritic Cell Motility
Mengwasser, Joerg ;  Babes, Liane ;  Cordes, Steffen ;  Mertlitz, Sarah ;  Riesner, Katarina ;  Shi, Yu ;  McGearey, Aleixandria ;  Kalupa, Martina ;  Reinheckel, Thomas ;  Penack, Olaf

HaupttitelCathepsin E Deficiency Ameliorates Graft-versus-Host Disease and Modifies Dendritic Cell Motility
AutorMengwasser, Joerg
AutorBabes, Liane
AutorCordes, Steffen
AutorMertlitz, Sarah
AutorRiesner, Katarina
AutorShi, Yu
AutorMcGearey, Aleixandria
AutorKalupa, Martina
AutorReinheckel, Thomas
AutorPenack, Olaf
Seitenzahl11 S.
Freie SchlagwörterGVHD; cathepsin E; dendritic cells; HSCT; motility
DDC610 Medizin und Gesundheit
Auch erschienen inFront. Immunol. - 8 (2017), Artikel Nr. 203
ZusammenfassungMicrobial 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 motility in 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.
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Fachbereich/EinrichtungMedizinische Fakultät Charité - Universitätsmedizin Berlin
Dokumententyp/-SammlungenWissenschaftlicher Artikel
RechteCreative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Erstellt am19.04.2017 - 10:24:47
Letzte Änderung19.04.2017 - 10:28:38
Statische URLhttp://edocs.fu-berlin.de/docs/receive/FUDOCS_document_000000026829