Pannexin1 channels are required for chemokine-mediated migration of CD4+ T lymphocytes: Role in inflammation and experimental autoimmune encephalomyelitis

Stephani Velasquez, Shaily Malik, Sarah E. Lutz, Eliana Scemes, Eliseo A. Eugenin

Research output: Contribution to journalArticle

16 Scopus citations

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 HIVinfection 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.

Original languageEnglish (US)
Pages (from-to)4338-4347
Number of pages10
JournalJournal of Immunology
Volume196
Issue number10
DOIs
StatePublished - May 15 2016

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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