What defines a chemokine?-The curious case of CXCL17

Chemotactic cytokines (chemokines) are a group of around 40 small proteins which share a similar protein fold and are well known for their ability to direct the migration of leukocytes to a variety of tissue locations. CXCL17 was the last member of the chemokine family to be assigned and was admitted to the family based on theoretical modelling of the CXCL17 structure and chemotactic activity for monocytes and dendritic cells. Of Interest, CXCL17 expression appears to be restricted to mucosal tissues such as the tongue, stomach and lung, suggestive of specific roles at these locations. A putative CXCL17 receptor, GPR35 was reportedly identified and mice deficient in CXCL17 were generated and characterised. More recently, however, some apparent contradictions regarding aspects of CXCL17 biology have been raised by ourselves and others. Notably, GPR35 appears to be a receptor for the serotonin metabolite 5-hydroxyindoleacetic acid rather than for CXCL17 and modelling of CXCL17 using a variety of platforms fails to identify a chemokine-like fold. In this article, we summarize the discovery of CXCL17 and discuss key papers describing the subsequent characterisation of this protein. Ultimately, we pose the question, 'What defines a chemokine?' (185 words)

Automated summary

CXCL17 is a chemotactic cytokine known for its ability to direct leukocyte migration. It is specifically expressed in mucosal tissues and may play specific roles in the tongue, stomach, and lung. Contrary to previous beliefs, recent studies suggest that GPR35 is not its receptor but rather related to the serotonin metabolite 5-hydroxyindoleacetic acid. Additionally, the structure of CXCL17 differs from typical chemokines. This article summarizes the discovery of CXCL17 and discusses the subsequent characterization of this protein.