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. 2021 Jun 7;12:664202. doi: 10.3389/fimmu.2021.664202

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Copyright © 2021 Cormican and Griffin

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Multiple signalling pathways are activated by both soluble and membrane-bound CX3CL1 (blue spheres) as outlined here. CX3CR1 is a G-protein coupled receptor linked to Gi and Gz proteins (8). Calcium release resulting in chemotaxis was demonstrated by Harrison et al. (29). CX3CL1 also contributes to intercellular adhesion through mechanisms which do not appear to be G-protein sensitive (5). Enhanced cellular survival is mediated by both the Akt and ERK pathways, including via transactivation of the EGFR receptor (16). CX3CL1 ligation of the CX3CR1 receptor also leads to nuclear translocation of transcription factors (30) including NFκB (31), CREB (32) and STAT (33) with resulting modulation of gene expression. Created with BioRender.com.