The Effect Of Physiological Laminar Shear Stress On The Immune Function Of Dendritic Cells

Objective: Dendritic cells(DCs) are the most powerful antigen presenting cells as now known, which play key roles in the initiation and amplifying of innate and adaptive immune response. During the whole processes of performing their immune regulatory function, DCs are always suffered the stimulation of shear stress(SS) derived from blood, interstitial and lymph fluids, but their responses to physiological fluid are still elusive. Therefore, the present study was focused on the effect of physiological laminar SS on the immune functions of DCs in order to further understand their biological functions. Methods: Monocytes from perphrial blood were induced grown into im DCs by rh IL-4 and rh GM-CSF, im DCs grown into m DCs at rh IFN-γ and LPS environment. The DCs loaded with 1, 5, 10, 15dyn/cm2 laminar flow SS by clone-to plate for 1, 3, 6, 12 h, then DC morphology were obervated under microscope and DC cytoskeleton distribution were investigated. The abilities of acquiring antigen were of DCs detected culture with FITC-dextran. In addition, the phenocytes CD11 c, CD40, CD80, CD83, CD86, CCR7, CD1 a, CD205 and HLA-DR and adhesion molecules CD18, CD11 a, CD54, CD62 P and CD106 were tested. The expression levels of genes were also demonstrated by genome-wide microarray, the DCs under static condition as control.Results: After SS, DC changed to round, the SS time longer and stronger SS, the shorter cell diameter and less dendritic protrusion(P<0.05). Furthermore, the organizations of F-actin in DCs were remodeled by SS. The abilities of endocytosis were reduced with SS at 3h. Moreover, the expressions of CD11 c, CD40, CD80, CD83, CD86, CCR7, CD1 a, CD205 and HLA-DR were downregulated by SS, and CD18, CD11 a, CD62 P and CD106 were also downregulation(P<0.05). The gene expression profiles showed that the 884 m RNAs, 25 mi RNAs and 811 lnc RNAs in im DCs and 848, 69 and 1056 in m DCs were changed by SS, respectively. Some of results obtained from microarray were confirmed by q RT-PCR, including m RNAs of IL-10,FOS,CCR2 and TLR2, micro RNAs has-mi R-532-3p and has-mi R-665. Conclusion: In conclusion, immune-related functions of DCs including im DCs and m DCs were significantly impaired by SS through remodeling the morphological characteristics and F-actincytosekeleton. It could be infered that SS could be a negative regulator for DCs-induced immune response, supporting the viewpoint of immuno-mechanobiology or mechanoimmunology. It is significant for further understanding the DCs biological behaviour and improving the clinical effiency of DCs-based immune therapy against cancer.?...