Pathological roles of the homeostatic chemokine CXCL12.

Abstract

CXCL12 is a CXC chemokine that traditionally has been classified as a homeostatic chemokine. It contributes to physiological processes such as embryogenesis, hematopoiesis and angiogenesis. In contrast to these homeostatic functions, increased expression of CXCL12 in general, or of a specific CXCL12 splicing variant has been demonstrated in various pathologies. In addition to this increased or differential transcription of CXCL12, also upregulation of its receptors CXC chemokine receptor 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3) contributes to the onset or progression of diseases. Moreover, posttranslational modification of CXCL12 during disease progression, through interaction with locally produced molecules or enzymes, also affects CXCL12 activity, adding further complexity. As CXCL12, CXCR4 and ACKR3 are broadly expressed, the number of pathologies wherein CXCL12 is involved is growing. In this review, the role of the CXCL12/CXCR4/ACKR3 axis will be discussed for the most prevalent pathologies. Administration of CXCL12-neutralizing antibodies or small-molecule antagonists of CXCR4 or ACKR3 delays disease onset or prevents disease progression in cancer, viral infections, inflammatory bowel diseases, rheumatoid arthritis and osteoarthritis, asthma and acute lung injury, amyotrophic lateral sclerosis and WHIM syndrome. On the other hand, CXCL12 has protective properties in Alzheimer's disease and multiple sclerosis, has a beneficial role in wound healing and has crucial homeostatic properties in general.

• Authors: Rik Janssens, Sofie Struyf, Paul Proost
• Journal: Cytokine & growth factor reviews (Cytokine Growth Factor Rev) Vol. 44 Pg. 51-68 (12 2018) ISSN: 1879-0305 [Electronic] England
• PMID: 30396776 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2018 Elsevier Ltd. All rights reserved.

Chemical References

• Chemokine CXCL12
• Receptors, CXCR4

Topics

• Animals
• Central Nervous System Diseases (metabolism)
• Chemokine CXCL12 (metabolism)
• Eye Diseases (metabolism)
• Humans
• Inflammatory Bowel Diseases (metabolism)
• Neoplasms
• Receptors, CXCR4 (metabolism)
• Respiratory Tract Diseases (metabolism)
• Rheumatic Diseases (metabolism)
• Virus Diseases (metabolism)