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The unique structural and functional features of CXCL12

Cellular & Molecular Immunology volume 15, pages 299–311 (2018)Cite this article

Abstract

The CXC chemokine CXCL12 is an important factor in physiological and pathological processes, including embryogenesis, hematopoiesis, angiogenesis and inflammation, because it activates and/or induces migration of hematopoietic progenitor and stem cells, endothelial cells and most leukocytes. Therefore, CXCL12 activity is tightly regulated at multiple levels. CXCL12 has the unique property of existing in six splice variants in humans, each having a specific tissue distribution and in vivo activity. Controlled splice variant transcription and mRNA stability determine the CXCL12 expression profile. CXCL12 fulfills its functions in homeostatic and pathological conditions by interacting with its receptors CXC chemokine receptor 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3) and by binding to glycosaminoglycans (GAGs) in tissues and on the endothelium to allow a proper presentation to passing leukocytes. Homodimerizaton and heterodimerization of CXCL12 and its receptors can alter their signaling activity, as exemplified by the synergy between CXCL12 and other chemokines in leukocyte migration assays. Receptor binding may also initiate CXCL12 internalization and its subsequent removal from the environment. Furthermore, CXCL12 activity is regulated by posttranslational modifications. Proteolytic removal of NH2- or COOH-terminal amino acids, citrullination of arginine residues by peptidyl arginine deiminases or nitration of tyrosine residues reduce CXCL12 activity. This review summarizes the interactions of CXCL12 with the cellular environment and discusses the different levels of CXCL12 activity regulation.

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Acknowledgements

This research was supported by the Interuniversity Attraction Poles Programme initiated by the Belgian Science Policy Office (I.A.P. Project 7/40), the Fund for Scientific Research of Flanders (FWO-Vlaanderen Projects G.0D25.17N, G.0764.14, and G.0D66.13), the Concerted Research Actions of the Regional Government of Flanders (GOA/12/017) and C1 funding (C16/17/010) of KU Leuven.

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  1. Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Immunology, KU Leuven, University of Leuven, B-3000, Leuven, Belgium

    Rik Janssens, Sofie Struyf & Paul Proost

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  1. Rik Janssens
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Correspondence to Paul Proost.

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Janssens, R., Struyf, S. & Proost, P. The unique structural and functional features of CXCL12. Cell Mol Immunol 15, 299–311 (2018). https://doi.org/10.1038/cmi.2017.107

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