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

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

J Invest Dermatol

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:

Published: August 2023

AI Article Synopsis

Article Abstract

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). 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.

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Source
http://dx.doi.org/10.1016/j.jid.2022.12.025DOI Listing

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