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. By employing a conditional Met-deficient mouse model (Metflox/flox) we addressed the role of Met-signaling in distinct steps of LC/dDC emigration from skin. Met deficiency did not prevent the decline in expression of the adhesion molecules E-cadherin and EpCAM in LC upon activation and consequently detachment from the surrounding tissue and migration towards dermis. However, Met-deficient LC failed to efficiently cross the extracellular matrix (ECM) rich basement membrane between epidermis and dermis. We found that Met deficiency severely impaired podosome formation in DC and concomitantly decreased proteolytic degradation of gelatin. 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. In contrast, 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.
Competing Interest Statement
The authors have declared no competing interest.