title: The atypical chemokine receptor ACKR2 suppresses Th17 responses to protein autoantigens.
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 in vivo. ACKR2 is also universally expressed by innate-like B cells, suppressing their responsiveness to the non-ACKR2 ligand CXCL13, and controlling their distribution in vivo. The role of ACKR2 in autoimmunity remains relatively unexplored, although Ackr2 deficiency reportedly lessens the clinical symptoms of experimental autoimmune encephalomyelitis induced by immunization with encephalogenic peptide (MOG(35-55)). 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 Ackr2-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(35-55)), and responses to protein antigen (collagen or MOG(1-125)) are characterized by elevated interleukin-17 production. Interestingly, after immunization with protein, but not peptide, antigen, Ackr2 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, Ackr2 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(+) B cells in lymph nodes draining the site of immunization.
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Chris A H
authors.initials: CA
authors.lastname: Hansell
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: MacLellan
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Rachel S
authors.initials: RS
authors.lastname: Oldham
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: James
authors.initials: J
authors.lastname: Doonan
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Katie J
authors.initials: KJ
authors.lastname: Chapple
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Elinor J R
authors.initials: EJ
authors.lastname: Anderson
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Linington
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Iain B
authors.initials: IB
authors.lastname: McInnes
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Robert J B
authors.initials: RJ
authors.lastname: Nibbs
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Carl S
authors.initials: CS
authors.lastname: Goodyear
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology; D001324:Autoantigens / Q000276:immunology*; D003094:Collagen / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007109:Immunity; D007114:Immunization; D020381:Interleukin-17 / Q000096:biosynthesis; D007596:Joints / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D018655:Lymphocyte Count; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D019707:Receptors, Chemokine / Q000172:deficiency / Q000378:metabolism*; D058504:Th17 Cells / Q000276:immunology*; D015854:Up-Regulation; D000097628:Chemokine Receptor D6
chemical_list: D000906:Antibodies; D001324:Autoantigens; D003094:Collagen; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D020381:Interleukin-17; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D019707:Receptors, Chemokine; C515709:Ackr2 protein, mouse; D000097628:Chemokine Receptor D6; C445081:myelin oligodendrocyte glycoprotein (35-55)