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Biomedicines 2015, 3(1), 138-148; doi:10.3390/biomedicines3010138

HGF/Met-Signaling Contributes to Immune Regulation by Modulating Tolerogenic and Motogenic Properties of Dendritic Cells

1
Department of Cell Biology, Institute for Biomedical Engineering, Medical Faculty, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany
2
Helmholtz Institute for Biomedical Engineering, RWTH Aachen University, Pauwelsstrasse 20, 52074 Aachen, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Zimmer Yitzhak
Received: 23 December 2014 / Revised: 6 February 2015 / Accepted: 13 February 2015 / Published: 3 March 2015
(This article belongs to the Special Issue New aspects of the Hepatocyte Growth Factor/c-Met System)
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Abstract

Hepatocyte growth factor (HGF)-signaling via Met can induce mitogenic, morphogenic, and motogenic activity in various cell types. Met expression in the immune system is limited to cells with antigen-presenting capacities, including dendritic cells (DCs). Thus, it appears highly conceivable that Met-signaling impacts on adaptive immune responses. However, the mechanisms by which HGF imparts its effects on immunological responses are not yet fully understood. DCs possess unique functionalities that are critically involved in controlling both tolerance and immunity. HGF conveys immunoregulatory functions, which strongly correlate with that of DCs orchestrating the apt immune response in inflammation. Therefore, this review focuses on the current knowledge of Met-signaling in DCs with specific emphasis on the morphogenic and motogenic activities. HGF has been identified to play a role in peripheral immune tolerance by directing DC differentiation towards a tolerogenic phenotype. In skin immunity, Met-signaling was shown to drive mobilization of DCs by regulating matrix metalloproteinase activities. This is strikingly reminiscent of the role of Met for regulating a cell fate program during embryonic development, wound healing, and in tumor invasion known as epithelial-mesenchymal transition (EMT). Thus, the concept emerges that an EMT program is executed by Met-signaling in DCs, which will be also discussed. View Full-Text
Keywords: Met; HGF; dendritic cells; Langerhans cells; immune tolerance; immune-based therapies; migration; MMPs; epithelial-mesenchymal transition Met; HGF; dendritic cells; Langerhans cells; immune tolerance; immune-based therapies; migration; MMPs; epithelial-mesenchymal transition
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Hübel, J.; Hieronymus, T. HGF/Met-Signaling Contributes to Immune Regulation by Modulating Tolerogenic and Motogenic Properties of Dendritic Cells. Biomedicines 2015, 3, 138-148.

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