Met-Signaling Controls Dendritic Cell Migration in Skin by Regulating Podosome Formation and Function.

Autor:	Hamouda AEI; Institute for Biomedical Engineering, Department of Cell Biology, RWTH Aachen University Clinic, Aachen, Germany; Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany., Schalla C; Institute for Biomedical Engineering, Department of Cell Biology, RWTH Aachen University Clinic, Aachen, Germany; Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany; Institute for Cell and Tumor Biology, RWTH Aachen University Clinic, Aachen, Germany., Sechi A; Institute for Biomedical Engineering, Department of Cell Biology, RWTH Aachen University Clinic, Aachen, Germany; Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany; Institute for Cell and Tumor Biology, RWTH Aachen University Clinic, Aachen, Germany., Zenke M; Institute for Biomedical Engineering, Department of Cell Biology, RWTH Aachen University Clinic, Aachen, Germany; Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany; Department of Hematology, Oncology, and Stem Cell Transplantation, RWTH Aachen University Clinic, Aachen, Germany., Schneider RK; Institute for Cell and Tumor Biology, RWTH Aachen University Clinic, Aachen, Germany., Hieronymus T; Institute for Biomedical Engineering, Department of Cell Biology, RWTH Aachen University Clinic, Aachen, Germany; Helmholtz-Institute for Biomedical Engineering, RWTH Aachen University, Aachen, Germany; Institute for Cell and Tumor Biology, RWTH Aachen University Clinic, Aachen, Germany. Electronic address: thomas.hieronymus@rwth-aachen.de.
Jazyk:	angličtina
Zdroj:	The Journal of investigative dermatology [J Invest Dermatol] 2023 Aug; Vol. 143 (8), pp. 1548-1558.e13. Date of Electronic Publication: 2023 Feb 21.
DOI:	10.1016/j.jid.2022.12.025
Abstrakt:	Signaling through the HGF receptor/Met in skin-resident Langerhans cells (LCs) and dermal dendritic cells (DCs) is essential for their emigration toward draining lymph nodes upon inflammation-induced activation. In this study, we addressed the role of Met signaling in distinct steps of LC/dermal DC emigration from the skin by employing a conditionally Met-deficient mouse model (Met f lox/flox ). We found that Met deficiency severely impaired podosome formation in DCs and concomitantly decreased the proteolytic degradation of gelatin. Accordingly, Met-deficient LCs failed to efficiently cross the extracellular matrix-rich basement membrane between the epidermis and the dermis. We further observed that HGF-dependent Met activation reduced the adhesion of bone marrow-derived LCs to various extracellular matrix factors and enhanced the motility of DCs in three-dimensional collagen matrices, which was not the case for Met-deficient LCs/DCs. We found no impact of Met signaling on the integrin-independent amoeboid migration of DCs in response to the CCR7 ligand CCL19. Collectively, our data show that the Met-signaling pathway regulates the migratory properties of DC in HGF-dependent and HGF-independent manners. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu