Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6

J. Schwarz, V. Bierbaum, K. Vaahtomeri, R. Hauschild, M. Brown, I. De Vries, A.F. Leithner, A. Reversat, J. Merrin, T. Tarrant, T. Bollenbach, M.K. Sixt, Current Biology 27 (2017) 1314–1325.

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Journal Article | Published | English
Abstract
Navigation of cells along gradients of guidance cues is a determining step in many developmental and immunological processes. Gradients can either be soluble or immobilized to tissues as demonstrated for the haptotactic migration of dendritic cells (DCs) toward higher concentrations of immobilized chemokine CCL21. To elucidate how gradient characteristics govern cellular response patterns, we here introduce an in vitro system allowing to track migratory responses of DCs to precisely controlled immobilized gradients of CCL21. We find that haptotactic sensing depends on the absolute CCL21 concentration and local steepness of the gradient, consistent with a scenario where DC directionality is governed by the signal-to-noise ratio of CCL21 binding to the receptor CCR7. We find that the conditions for optimal DC guidance are perfectly provided by the CCL21 gradients we measure in vivo. Furthermore, we find that CCR7 signal termination by the G-protein-coupled receptor kinase 6 (GRK6) is crucial for haptotactic but dispensable for chemotactic CCL21 gradient sensing in vitro and confirm those observations in vivo. These findings suggest that stable, tissue-bound CCL21 gradients as sustainable “roads” ensure optimal guidance in vivo.
Publishing Year
Date Published
2017-05-09
Journal Title
Current Biology
Volume
27
Issue
9
Page
1314 - 1325
ISSN
IST-REx-ID

Cite this

Schwarz J, Bierbaum V, Vaahtomeri K, et al. Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6. Current Biology. 2017;27(9):1314-1325. doi:10.1016/j.cub.2017.04.004
Schwarz, J., Bierbaum, V., Vaahtomeri, K., Hauschild, R., Brown, M., De Vries, I., … Sixt, M. K. (2017). Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6. Current Biology, 27(9), 1314–1325. https://doi.org/10.1016/j.cub.2017.04.004
Schwarz, Jan, Veronika Bierbaum, Kari Vaahtomeri, Robert Hauschild, Markus Brown, Ingrid De Vries, Alexander F Leithner, et al. “Dendritic Cells Interpret Haptotactic Chemokine Gradients in a Manner Governed by Signal to Noise Ratio and Dependent on GRK6.” Current Biology 27, no. 9 (2017): 1314–25. https://doi.org/10.1016/j.cub.2017.04.004.
J. Schwarz et al., “Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6,” Current Biology, vol. 27, no. 9, pp. 1314–1325, 2017.
Schwarz J, Bierbaum V, Vaahtomeri K, Hauschild R, Brown M, De Vries I, Leithner AF, Reversat A, Merrin J, Tarrant T, Bollenbach T, Sixt MK. 2017. Dendritic cells interpret haptotactic chemokine gradients in a manner governed by signal to noise ratio and dependent on GRK6. Current Biology. 27(9), 1314–1325.
Schwarz, Jan, et al. “Dendritic Cells Interpret Haptotactic Chemokine Gradients in a Manner Governed by Signal to Noise Ratio and Dependent on GRK6.” Current Biology, vol. 27, no. 9, Cell Press, 2017, pp. 1314–25, doi:10.1016/j.cub.2017.04.004.

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