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The atypical chemokine receptor CCX-CKR scavenges homeostatic chemokines in circulation and tissues and suppresses Th17 responses
- Source :
- Blood. 116(20)
- Publication Year :
- 2010
-
Abstract
- Our previous in vitro studies led to proposals that the atypical chemokine receptor CCX-CKR is a scavenger of CCR7 ligand homeostatic chemokines. In the present study, we generated CCX-CKR−/− mice and confirm this scavenger function in vivo. Compared with wild-type mice, CCX-CKR−/− have a 5-fold increase in the level of CCL21 protein in blood, and 2- to 3-fold increases in CCL19 and CCL21 in peripheral lymph nodes. The effect of these protein increases on immunity was investigated after immunization with MOG35-55 peptide emulsified in complete Freund adjuvant (CFA). The subsequent characteristic paralysis develops with enhanced kinetics and severity in CCX-CKR−/− versus wild-type mice. Despite this effect, antigen-specific immune responses in the draining lymph nodes are diminished in CCX-CKR−/− mice. Instead, the earlier onset of disease is associated with enhanced T-cell priming in the CCX-CKR−/− spleen and a skewing of CD4+ T-cell responses toward Th17 rather than Th1. This observation correlates with increased expression of IL-23 in the CCX-CKR−/− spleen and increased CCL21 levels in the central nervous system postimmunization. The early onset of disease in CCX-CKR−/− mice is reversed by systemic administration of neutralizing anti-CCL21 antibodies. Thus, by regulating homeostatic chemokine bioavailability, CCX-CKR influences the localization, kinetics, and nature of adaptive immune responses in vivo.
- Subjects :
- Central Nervous System
medicine.medical_specialty
Chemokine
Encephalomyelitis, Autoimmune, Experimental
Immunology
C-C chemokine receptor type 7
Spleen
Biochemistry
Interleukin-23
Chemokine receptor
Mice
Immune system
Cross-Priming
Neutralization Tests
Internal medicine
medicine
Animals
Homeostasis
Receptor
biology
Chemokine CCL21
CCL19
Cell Biology
Hematology
Th1 Cells
Mice, Inbred C57BL
Kinetics
medicine.anatomical_structure
Endocrinology
Organ Specificity
biology.protein
Chemokine CCL19
Th17 Cells
Receptors, Chemokine
Lymph Nodes
CCL21
Subjects
Details
- ISSN :
- 15280020
- Volume :
- 116
- Issue :
- 20
- Database :
- OpenAIRE
- Journal :
- Blood
- Accession number :
- edsair.doi.dedup.....f26632483c0f76446c0702e498ec477b