Role of Atypical Chemokine Receptors in Microglial Activation and Polarization
Inflammatory reactions occurring in the central nervous system (CNS), known as neuroinflammation, are key components of the pathogenic mechanisms underlying several neurological diseases. The chemokine system plays a crucial role in the recruitment and activation of immune and non-immune cells in th...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-05-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fnagi.2017.00148/full |
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| author | Valentina Salvi Francesca Sozio Francesca Sozio Silvano Sozzani Silvano Sozzani Annalisa Del Prete Annalisa Del Prete |
| author_facet | Valentina Salvi Francesca Sozio Francesca Sozio Silvano Sozzani Silvano Sozzani Annalisa Del Prete Annalisa Del Prete |
| author_sort | Valentina Salvi |
| collection | DOAJ |
| description | Inflammatory reactions occurring in the central nervous system (CNS), known as neuroinflammation, are key components of the pathogenic mechanisms underlying several neurological diseases. The chemokine system plays a crucial role in the recruitment and activation of immune and non-immune cells in the brain, as well as in the regulation of microglia phenotype and function. Chemokines belong to a heterogeneous family of chemotactic agonists that signal through the interaction with G protein-coupled receptors (GPCRs). Recently, a small subset of chemokine receptors, now identified as “atypical chemokine receptors” (ACKRs), has been described. These receptors lack classic GPCR signaling and chemotactic activity and are believed to limit inflammation through their ability to scavenge chemokines at the inflammatory sites. Recent studies have highlighted a role for ACKRs in neuroinflammation. However, in the CNS, the role of ACKRs seems to be more complex than the simple control of inflammation. For instance, CXCR7/ACKR3 was shown to control T cell trafficking through the regulation of CXCL12 internalization at CNS endothelial barriers. Furthermore, D6/ACKR2 KO mice were protected in a model of experimental autoimmune encephalomyelitis (EAE). D6/ACKR2 KO showed an abnormal accumulation of dendritic cells at the immunization and a subsequent impairment in T cell priming. Finally, CCRL2, an ACKR-related protein, was shown to play a role in the control of the resolution phase of EAE. Indeed, CCRL2 KO mice showed exacerbated, non-resolving disease with protracted inflammation and increased demyelination. This phenotype was associated with increased microglia and macrophage activation markers and imbalanced M1 vs. M2 polarization. This review will summarize the current knowledge on the role of the ACKRs in neuroinflammation with a particular attention to their role in microglial polarization and function. |
| first_indexed | 2024-12-17T13:11:46Z |
| format | Article |
| id | doaj.art-ce9a88df047f4477b36e05b83288d442 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-17T13:11:46Z |
| publishDate | 2017-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-ce9a88df047f4477b36e05b83288d4422022-12-21T21:47:05ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652017-05-01910.3389/fnagi.2017.00148268480Role of Atypical Chemokine Receptors in Microglial Activation and PolarizationValentina Salvi0Francesca Sozio1Francesca Sozio2Silvano Sozzani3Silvano Sozzani4Annalisa Del Prete5Annalisa Del Prete6Department of Molecular and Translational Medicine, University of BresciaBrescia, ItalyDepartment of Molecular and Translational Medicine, University of BresciaBrescia, ItalyIRCCS-Humanitas Clinical and Research CenterRozzano-Milano, ItalyDepartment of Molecular and Translational Medicine, University of BresciaBrescia, ItalyIRCCS-Humanitas Clinical and Research CenterRozzano-Milano, ItalyDepartment of Molecular and Translational Medicine, University of BresciaBrescia, ItalyIRCCS-Humanitas Clinical and Research CenterRozzano-Milano, ItalyInflammatory reactions occurring in the central nervous system (CNS), known as neuroinflammation, are key components of the pathogenic mechanisms underlying several neurological diseases. The chemokine system plays a crucial role in the recruitment and activation of immune and non-immune cells in the brain, as well as in the regulation of microglia phenotype and function. Chemokines belong to a heterogeneous family of chemotactic agonists that signal through the interaction with G protein-coupled receptors (GPCRs). Recently, a small subset of chemokine receptors, now identified as “atypical chemokine receptors” (ACKRs), has been described. These receptors lack classic GPCR signaling and chemotactic activity and are believed to limit inflammation through their ability to scavenge chemokines at the inflammatory sites. Recent studies have highlighted a role for ACKRs in neuroinflammation. However, in the CNS, the role of ACKRs seems to be more complex than the simple control of inflammation. For instance, CXCR7/ACKR3 was shown to control T cell trafficking through the regulation of CXCL12 internalization at CNS endothelial barriers. Furthermore, D6/ACKR2 KO mice were protected in a model of experimental autoimmune encephalomyelitis (EAE). D6/ACKR2 KO showed an abnormal accumulation of dendritic cells at the immunization and a subsequent impairment in T cell priming. Finally, CCRL2, an ACKR-related protein, was shown to play a role in the control of the resolution phase of EAE. Indeed, CCRL2 KO mice showed exacerbated, non-resolving disease with protracted inflammation and increased demyelination. This phenotype was associated with increased microglia and macrophage activation markers and imbalanced M1 vs. M2 polarization. This review will summarize the current knowledge on the role of the ACKRs in neuroinflammation with a particular attention to their role in microglial polarization and function.http://journal.frontiersin.org/article/10.3389/fnagi.2017.00148/fullchemokine receptorsneuroinflammationmicrogliaatypical chemokine receptorsCCRL2 |
| spellingShingle | Valentina Salvi Francesca Sozio Francesca Sozio Silvano Sozzani Silvano Sozzani Annalisa Del Prete Annalisa Del Prete Role of Atypical Chemokine Receptors in Microglial Activation and Polarization Frontiers in Aging Neuroscience chemokine receptors neuroinflammation microglia atypical chemokine receptors CCRL2 |
| title | Role of Atypical Chemokine Receptors in Microglial Activation and Polarization |
| title_full | Role of Atypical Chemokine Receptors in Microglial Activation and Polarization |
| title_fullStr | Role of Atypical Chemokine Receptors in Microglial Activation and Polarization |
| title_full_unstemmed | Role of Atypical Chemokine Receptors in Microglial Activation and Polarization |
| title_short | Role of Atypical Chemokine Receptors in Microglial Activation and Polarization |
| title_sort | role of atypical chemokine receptors in microglial activation and polarization |
| topic | chemokine receptors neuroinflammation microglia atypical chemokine receptors CCRL2 |
| url | http://journal.frontiersin.org/article/10.3389/fnagi.2017.00148/full |
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