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Cell Rep. 2016 Aug 2;16(5):1339-1351. doi: 10.1016/j.celrep.2016.06.065. Epub 2016 Jul 21.

Inflammatory Th17 Cells Express Integrin αvβ3 for Pathogenic Function.

Author information

1
Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, 3500 Terrace Street, Pittsburgh, PA 15261, USA.
2
Benaroya Research Institute, Seattle, WA 98101, USA.
3
Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh, 3500 Terrace Street, Pittsburgh, PA 15261, USA. Electronic address: mandymcgeachy@pitt.edu.

Abstract

Interleukin-23 (IL-23) is required for inflammatory Th17 cell function in experimental autoimmune encephalomyelitis (EAE), and IL-23 blockade reduces the number of effector Th17 cells in the CNS. We report that pro-inflammatory Th17 cells express high integrin β3 that is IL-23 dependent. Integrin β3 was not upregulated on all activated T cells; rather, integrin β3 was upregulated along with its functional partner integrin αv on effector Th17 cells and "ex-Th17" cells, and αvβ3(hi) RORγt(+) cells expanded during EAE. Integrin αvβ3 inhibitors ameliorated clinical signs of EAE, and integrin β3 deficiency on CD4(+) T cells alone was sufficient to block EAE induction. Furthermore, integrin-β3-deficient Th17 cells, but not Th1 cells, were impaired in their ability to induce EAE. Integrin β3(-/-) T cells induced smaller demyelinated lesions and showed reduced spread and accumulation within the CNS, corresponding with impaired extracellular-matrix-mediated migration. Hence, integrin β3 is required for Th17 cell-mediated autoimmune CNS inflammation.

PMID:
27452457
PMCID:
PMC5627357
DOI:
10.1016/j.celrep.2016.06.065
[Indexed for MEDLINE]
Free PMC Article

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