Author:
Kang Ji-Hun,Lee Hyun Joo,Kim Ok-Hyeon,Yun Yong Ju,Seo Young-Jin,Lee Hyun Jung
Abstract
AbstractMechanical forces are pervasive in the inflammatory site where dendritic cells (DCs) are activated to migrate into draining lymph nodes. For example, fluid shear stress modulates the movement patterns of DCs, including directness and forward migration indices (FMIs), without chemokine effects. However, little is known about the effects of biomechanical forces on the activation of DCs. Accordingly, here we fabricated a microfluidics system to assess how biomechanical forces affect the migration and activity of DCs during inflammation. Based on the structure of edema, we proposed and experimentally analyzed a novel concept for a microchip model that mimicked such vascular architecture. The intensity of shear stress generated in our engineered chip was found as 0.2–0.6 dyne/cm2 by computational simulation; this value corresponded to inflammation in tissues. In this platform, the directness and FMIs of DCs were significantly increased, whereas the migration velocity of DCs was not altered by shear stress, indicating that mechanical stimuli influenced DC migration. Moreover, DCs with shear stress showed increased expression of the DC activation markers MHC class I and CD86 compared with DCs under static conditions. Taken together, these data suggest that the biomechanical forces are important to regulate the migration and activity of DCs.
Funder
National Research Foundation of Korea
Korea University Grant
Publisher
Springer Science and Business Media LLC
Reference49 articles.
1. Elbe, A. et al. Maturational steps of bone marrow-derived dendritic murine epidermal cells. Phenotypic and functional studies on Langerhans cells and Thy-1+ dendritic epidermal cells in the perinatal period. J. Immunol. 143, 2431–2438 (1989).
2. Alvarez, D., Vollmann, E. H. & von Andrian, U. H. Mechanisms and consequences of dendritic cell migration. Immunity 29, 325–342. https://doi.org/10.1016/j.immuni.2008.08.006 (2008).
3. Helft, J. et al. GM-CSF mouse bone marrow cultures comprise a heterogeneous population of CD11c(+)MHCII(+) macrophages and dendritic cells. Immunity 42, 1197–1211. https://doi.org/10.1016/j.immuni.2015.05.018 (2015).
4. Tamoutounour, S. et al. Origins and functional specialization of macrophages and of conventional and monocyte-derived dendritic cells in mouse skin. Immunity 39, 925–938. https://doi.org/10.1016/j.immuni.2013.10.004 (2013).
5. Rescigno, M., Martino, M., Sutherland, C. L., Gold, M. R. & Ricciardi-Castagnoli, P. Dendritic cell survival and maturation are regulated by different signaling pathways. J. Exp. Med. 188, 2175–2180. https://doi.org/10.1084/jem.188.11.2175 (1998).
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