Shape and function of interstitial chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic endothelium

Vaahtomeri K, Moussion C, Hauschild R, Sixt MK. 2021. Shape and function of interstitial chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic endothelium. Frontiers in Immunology. 12, 630002.

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Journal Article | Published | English

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Abstract
Gradients of chemokines and growth factors guide migrating cells and morphogenetic processes. Migration of antigen-presenting dendritic cells from the interstitium into the lymphatic system is dependent on chemokine CCL21, which is secreted by endothelial cells of the lymphatic capillary, binds heparan sulfates and forms gradients decaying into the interstitium. Despite the importance of CCL21 gradients, and chemokine gradients in general, the mechanisms of gradient formation are unclear. Studies on fibroblast growth factors have shown that limited diffusion is crucial for gradient formation. Here, we used the mouse dermis as a model tissue to address the necessity of CCL21 anchoring to lymphatic capillary heparan sulfates in the formation of interstitial CCL21 gradients. Surprisingly, the absence of lymphatic endothelial heparan sulfates resulted only in a modest decrease of CCL21 levels at the lymphatic capillaries and did neither affect interstitial CCL21 gradient shape nor dendritic cell migration toward lymphatic capillaries. Thus, heparan sulfates at the level of the lymphatic endothelium are dispensable for the formation of a functional CCL21 gradient.
Publishing Year
Date Published
2021-02-25
Journal Title
Frontiers in Immunology
Acknowledgement
This work was supported by Sigrid Juselius fellowship (KV), University of Helsinki 3-year research grant (KV), Academy of Finland Research fellow funding (315710, to KV), the European Research Council (ERC CoG 724373 to MS), and by the Austrian Science foundation (FWF) (Y564-B12 START award to MS). Taija Mäkinen is acknowledged for providing Prox1CreERT2 transgenic mice and Yu Yamaguchi for providing the conditional Ext1 mouse strain.
Volume
12
Article Number
630002
eISSN
IST-REx-ID

Cite this

Vaahtomeri K, Moussion C, Hauschild R, Sixt MK. Shape and function of interstitial chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic endothelium. Frontiers in Immunology. 2021;12. doi:10.3389/fimmu.2021.630002
Vaahtomeri, K., Moussion, C., Hauschild, R., & Sixt, M. K. (2021). Shape and function of interstitial chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic endothelium. Frontiers in Immunology. Frontiers. https://doi.org/10.3389/fimmu.2021.630002
Vaahtomeri, Kari, Christine Moussion, Robert Hauschild, and Michael K Sixt. “Shape and Function of Interstitial Chemokine CCL21 Gradients Are Independent of Heparan Sulfates Produced by Lymphatic Endothelium.” Frontiers in Immunology. Frontiers, 2021. https://doi.org/10.3389/fimmu.2021.630002.
K. Vaahtomeri, C. Moussion, R. Hauschild, and M. K. Sixt, “Shape and function of interstitial chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic endothelium,” Frontiers in Immunology, vol. 12. Frontiers, 2021.
Vaahtomeri K, Moussion C, Hauschild R, Sixt MK. 2021. Shape and function of interstitial chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic endothelium. Frontiers in Immunology. 12, 630002.
Vaahtomeri, Kari, et al. “Shape and Function of Interstitial Chemokine CCL21 Gradients Are Independent of Heparan Sulfates Produced by Lymphatic Endothelium.” Frontiers in Immunology, vol. 12, 630002, Frontiers, 2021, doi:10.3389/fimmu.2021.630002.
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