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J Immunol. 2016 May 15;196(10):4338-47. doi: 10.4049/jimmunol.1502440. Epub 2016 Apr 13.

Pannexin1 Channels Are Required for Chemokine-Mediated Migration of CD4+ T Lymphocytes: Role in Inflammation and Experimental Autoimmune Encephalomyelitis.

Author information

1
Public Health Research Institute, Rutgers New Jersey Medical School, Rutgers The State University of New Jersey, Newark, NJ 07103; Department of Microbiology, Biochemistry, and Molecular Genetics, Rutgers New Jersey Medical School, Rutgers The State University of New Jersey, Newark, NJ 07103;
2
Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697; and.
3
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461.
4
Public Health Research Institute, Rutgers New Jersey Medical School, Rutgers The State University of New Jersey, Newark, NJ 07103; Department of Microbiology, Biochemistry, and Molecular Genetics, Rutgers New Jersey Medical School, Rutgers The State University of New Jersey, Newark, NJ 07103; eliseo.eugenin@rutgers.edu.

Abstract

Pannexin1 (Panx1) channels are large high conductance channels found in all vertebrates that can be activated under several physiological and pathological conditions. Our published data indicate that HIV infection results in the extended opening of Panx1 channels (5-60 min), allowing for the secretion of ATP through the channel pore with subsequent activation of purinergic receptors, which facilitates HIV entry and replication. In this article, we demonstrate that chemokines, which bind CCR5 and CXCR4, especially SDF-1α/CXCL12, result in a transient opening (peak at 5 min) of Panx1 channels found on CD4(+) T lymphocytes, which induces ATP secretion, focal adhesion kinase phosphorylation, cell polarization, and subsequent migration. Increased migration of immune cells is key for the pathogenesis of several inflammatory diseases including multiple sclerosis (MS). In this study, we show that genetic deletion of Panx1 reduces the number of the CD4(+) T lymphocytes migrating into the spinal cord of mice subjected to experimental autoimmune encephalomyelitis, an animal model of MS. Our results indicate that opening of Panx1 channels in response to chemokines is required for CD4(+) T lymphocyte migration, and we propose that targeting Panx1 channels could provide new potential therapeutic approaches to decrease the devastating effects of MS and other inflammatory diseases.

PMID:
27076682
PMCID:
PMC4918517
DOI:
10.4049/jimmunol.1502440
[Indexed for MEDLINE]
Free PMC Article

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