期刊
IMMUNITY
卷 54, 期 8, 页码 1715-+出版社
CELL PRESS
DOI: 10.1016/j.immuni.2021.06.014
关键词
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类别
资金
- NHLBI [P01HL120840]
- NIGMS [R35GM122542]
- Center for Cell Clearance, University of Virginia School of Medicine
- FWO, Belgium
- FWO [3083753-DECODE]
- NIAID [R21 AI139967, R21 AI135455]
- NIH T32 Pharmacology Training Grant [T32GM007055]
- Wellcome Trust [206566/Z/17/Z]
- Ministry of Science and Technology Taiwan [108-2320-B-007-007-MY2]
- Wellcome Trust [206566/Z/17/Z] Funding Source: Wellcome Trust
The nucleotide release channel Panx1 plays an immunoregulatory role in T cell crosstalk during allergic airway inflammation, aiding in the suppression of disease progression. Mechanistic studies have shown the importance of Panx1-dependent Treg:Teff cell communication in restricting airway disease.
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.
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