CCL17 in Inflammation and Pain.

Abstract

It has been reported that a GM-CSF→CCL17 pathway, originally identified in vitro in macrophage lineage populations, is implicated in the control of inflammatory pain, as well as arthritic pain and disease. We explore, in this study and in various inflammation models, the cellular CCL17 expression and its GM-CSF dependence as well as the function of CCL17 in inflammation and pain. This study used models allowing the convenient cell isolation from Ccl17E/+ reporter mice; it also exploited both CCL17-dependent and unique CCL17-driven inflammatory pain and arthritis models, the latter permitting a radiation chimera approach to help identify the CCL17 responding cell type(s) and the mediators downstream of CCL17 in the control of inflammation and pain. We present evidence that 1) in the particular inflammation models studied, CCL17 expression is predominantly in macrophage lineage populations and is GM-CSF dependent, 2) for its action in arthritic pain and disease development, CCL17 acts on CCR4+ non-bone marrow-derived cells, and 3) for inflammatory pain development in which a GM-CSF→CCL17 pathway appears critical, nerve growth factor, CGRP, and substance P all appear to be required.

• Authors: Kevin M-C Lee, Andrew Jarnicki, Adrian Achuthan, Andrew J Fleetwood, Gary P Anderson, Christian Ellson, Maria Feeney, Louise K Modis, Julia E Smith, John A Hamilton, Andrew Cook
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 205 Issue 1 Pg. 213-222 (07 01 2020) ISSN: 1550-6606 [Electronic] United States
• PMID: 32461237 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 by The American Association of Immunologists, Inc.

Chemical References

• Ccl17 protein, mouse
• Chemokine CCL17
• Substance P
• Granulocyte-Macrophage Colony-Stimulating Factor
• Nerve Growth Factor
• Calcitonin Gene-Related Peptide

Topics

• Animals
• Arthritis, Experimental (complications, immunology, pathology)
• Calcitonin Gene-Related Peptide (metabolism)
• Chemokine CCL17 (genetics, metabolism)
• Genes, Reporter (genetics)
• Granulocyte-Macrophage Colony-Stimulating Factor (metabolism)
• Humans
• Mice
• Mice, Transgenic
• Nerve Growth Factor (metabolism)
• Pain (diagnosis, immunology, pathology)
• Pain Measurement
• Peritonitis (complications, immunology, pathology)
• Pneumonia (complications, immunology, pathology)
• Signal Transduction (immunology)
• Substance P (metabolism)