The atypical chemokine receptor ACKR2 suppresses Th17 responses to protein autoantigens

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)

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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
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 > Institute of Infection Immunity and Inflammation
Journal Name:Immunology and Cell Biology
Publisher:Nature Publishing Group
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

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