Pannexin 1 channels facilitate communication between T cells to restrict the severity of airway inflammation

Christopher B. Medina, Yu Hsin Chiu, Marta E. Stremska, Christopher D. Lucas, Ivan Poon, Kenneth S. Tung, Michael R. Elliott, Bimal Desai, Ulrike M. Lorenz, Douglas A. Bayliss, Kodi S. Ravichandran

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Allergic airway inflammation is driven by type-2 CD4+ T cell inflammatory responses. We uncover an immunoregulatory role for the nucleotide release channel, Panx1, in T cell crosstalk during airway disease. Inverse correlations between Panx1 and asthmatics and our mouse models revealed the necessity, specificity, and sufficiency of Panx1 in T cells to restrict inflammation. Global Panx1−/− mice experienced exacerbated airway inflammation, and T-cell-specific deletion phenocopied Panx1−/− mice. A transgenic designed to re-express Panx1 in T cells reversed disease severity in global Panx1−/− mice. Panx1 activation occurred in pro-inflammatory T effector (Teff) and inhibitory T regulatory (Treg) cells and mediated the extracellular-nucleotide-based Treg-Teff crosstalk required for suppression of Teff cell proliferation. Mechanistic studies identified a Salt-inducible kinase-dependent phosphorylation of Panx1 serine 205 important for channel activation. A genetically targeted mouse expressing non-phosphorylatable Panx1S205A phenocopied the exacerbated inflammation in Panx1−/− mice. These data identify Panx1-dependent Treg:Teff cell communication in restricting airway disease.

Original languageEnglish
Pages (from-to)1715-1727.e7
JournalImmunity
Volume54
Issue number8
DOIs
StatePublished - Aug 10 2021

Keywords

  • Pannexin 1, extracellular ATP, lung, asthma, airway inflammation, T regulatory cell, T effector cell, Salt-inducible kinase, CD4 T cell, adenosine

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