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bioRxiv · 10.1101/2021.04.28.441791

Met-signaling controls Dendritic Cell migration by regulating podosome formation and function

Hamouda, A. E. I.·Schalla, C.·Sechi, A.·Zenke, M.·Hieronymus, T.
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Abstract

Signaling by the HGF receptor/Met in skin-resident Langerhans cells (LC) and dermal dendritic cells (dDC) is essential for their emigration toward draining lymph nodes upon inflammation-induced activation. Here we addressed the role of Met-signaling in distinct steps of LC/dDC emigration from skin by employing a conditional Met-deficient mouse model (Metflox/flox). We found that Met deficiency severely impaired podosome formation in DC and concomitantly decreased proteolytic degradation of gelatin. Accordingly, Met-deficient LC failed to efficiently cross the extracellular matrix (ECM) rich basement membrane between epidermis and dermis. We further observed that Met-signaling by HGF reduced adhesion of bone marrow-derived LC to various ECM factors and enhanced the motility of Met-signaling competent DC in a 3D collagen matrix, which was not the case for Met-deficient LC/DC. We found no impact of Met-signaling on the integrin-independent amoeboid migration of DC in response to the CCR7 chemokine 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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Hamouda, A. E. I., Schalla, C., Sechi, A., Zenke, M., Hieronymus, T.. 2021-04-28. Met-signaling controls Dendritic Cell migration by regulating podosome formation and function. https://doi.org/10.1101/2021.04.28.441791

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