Hansell, C. A., MacLellan, L. M., Oldham, R. S., Doonan, J., Chapple, K. J., Anderson, E. J., Linington, C. , McInnes, I. B. , Nibbs, R. J. and Goodyear, C. S. (2015) The atypical chemokine receptor ACKR2 suppresses Th17 responses to protein autoantigens. Immunology and Cell Biology, 93(2), pp. 167-176. (doi: 10.1038/icb.2014.90) (PMID:25348934) (PMCID:PMC4340511)
|
Text
98798.pdf - Published Version Available under License Creative Commons Attribution. 1MB |
Abstract
Chemokine-directed leukocyte migration is a critical component of all innate and adaptive immune responses. The atypical chemokine receptor ACKR2 is expressed by lymphatic endothelial cells and scavenges pro-inflammatory CC chemokines to indirectly subdue leukocyte migration. This contributes to the resolution of acute inflammatory responses <i>in vivo</i>. ACKR2 is also universally expressed by innate-like B cells, suppressing their responsiveness to the non-ACKR2 ligand CXCL13, and controlling their distribution <i>in vivo</i>. The role of ACKR2 in autoimmunity remains relatively unexplored, although <i>Ackr2</i> deficiency reportedly lessens the clinical symptoms of experimental autoimmune encephalomyelitis induced by immunization with encephalogenic peptide (MOG<sub>35–55</sub>). This was attributed to poor T-cell priming stemming from the defective departure of dendritic cells from the site of immunization. However, we report here that <i>Ackr2</i>-deficient mice, on two separate genetic backgrounds, are not less susceptible to autoimmunity induced by immunization, and in some cases develop enhanced clinical symptoms. Moreover, ACKR2 deficiency does not suppress T-cell priming in response to encephalogenic peptide (MOG<sub>35–55</sub>), and responses to protein antigen (collagen or MOG<sub>1–125</sub>) are characterized by elevated interleukin-17 production. Interestingly, after immunization with protein, but not peptide, antigen, <i>Ackr2</i> deficiency was also associated with an increase in lymph node B cells expressing granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine that enhances T helper type 17 (Th17) cell development and survival. Thus, <i>Ackr2</i> deficiency does not suppress autoreactive T-cell priming and autoimmune pathology, but can enhance T-cell polarization toward Th17 cells and increase the abundance of GM-CSF<sup>+</sup> B cells in lymph nodes draining the site of immunization.
Item Type: | Articles |
---|---|
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | McInnes, Professor Iain and Chapple, Dr Katie and Hansell, Dr Chris and Nibbs, Professor Rob and Linington, Professor Christopher and Maclellan, Dr Lindsay and Goodyear, Professor Carl and Anderson, Dr Elinor |
Authors: | Hansell, C. A., MacLellan, L. M., Oldham, R. S., Doonan, J., Chapple, K. J., Anderson, E. J., Linington, C., McInnes, I. B., Nibbs, R. J., and Goodyear, C. S. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Journal Name: | Immunology and Cell Biology |
Publisher: | Nature Publishing Group |
ISSN: | 0818-9641 |
ISSN (Online): | 1440-1711 |
Copyright Holders: | Copyright © 2014 The Authors |
First Published: | First published in Immunology and Cell Biology 93(2):167-176 |
Publisher Policy: | Reproduced under a Creative Commons License |
University Staff: Request a correction | Enlighten Editors: Update this record