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- W4313360225 abstract "Abstract Cytokines must diffuse between immune synapses, to neighboring cells, and across the lymph node in order to propagate specific immune responses. However, cytokine diffusion in the tissue environment has never been measured, making it difficult to model cell-cell signaling or the localization of cytokine therapeutics. Here, we analyzed the diffusion of TNF-α, IFN-γ, and IL-2, selected because they have central roles in immunity, they represent two different structural classes, and they vary in molecular weight and multimerization. We utilized a microfluidic platform to deliver picogram quantities of fluorescently labelled cytokines to specific regions of 300-μm thick slices of live murine lymph node tissue ex vivo and analyzed spread by fluorescent microscopy. The analysis method was compared to FRAP and microinjection techniques by analyzing diffusion of 10 kDa and 40 kDa Dextrans in both agarose and tissue slices. With the device, we were able to analyze diffusion of cytokines within the B-cell and T-cell zones of the tissue separately. On average, both TNF-α and IFN-γ diffused at the same rate in both the T-cell and B-cell zone (TNF-α: 2.5 ± 0.8 and 2.5 ± 1.6 × 10−7 cm2/s and IFN-γ: 6.0 ± 1.8 and 4.9 ± 1.5 × 10−7 cm2/s respectively, n = 7–9, p > 0.05); however, IL-2 diffused more rapidly in the T-cell zone (8.1 ±1.1 × 10−7 cm2/s, n = 7–8) than in the B-cell zone (4.5 ± 0.3 × 10−7 cm2/s, n = 7–8) yet the difference was not significant (p>0.05). Variation in diffusion between different zones suggests that cytokines interact differently within specific environments. This data provides the first diffusional analysis of cytokines in intact lymph node tissue and validates a new method to enhance the understanding of cell signaling kinetics." @default.
- W4313360225 created "2023-01-06" @default.
- W4313360225 creator A5003119785 @default.
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- W4313360225 date "2017-05-01" @default.
- W4313360225 modified "2023-09-27" @default.
- W4313360225 title "Diffusional analysis of cytokines in lymph node tissue on a microfluidic chip" @default.
- W4313360225 doi "https://doi.org/10.4049/jimmunol.198.supp.63.2" @default.
- W4313360225 hasPublicationYear "2017" @default.
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