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PLoS Biol. 2020 Mar 23;18(3):e3000646. doi: 10.1371/journal.pbio.3000646. eCollection 2020 Mar.

IL-23 signaling regulation of pro-inflammatory T-cell migration uncovered by phosphoproteomics.

Author information

1
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid (CSIC/UAM), Madrid, Spain.
2
Departamento de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
3
Instituto de Investigación Sanitaria del Hospital Universitario de La Princesa, Universidad Autonoma de Madrid, Madrid, Spain.

Abstract

Interleukin 23 (IL-23) triggers pathogenic features in pro-inflammatory, IL-17-secreting T cells (Th17 and Tγδ17) that play a key role in the development of inflammatory diseases. However, the IL-23 signaling cascade remains largely undefined. Here, we used quantitative phosphoproteomics to characterize IL-23 signaling in primary murine Th17 cells. We quantified 6,888 phosphorylation sites in Th17 cells and found 168 phosphorylations regulated upon IL-23 stimulation. IL-23 increased the phosphorylation of the myosin regulatory light chain (RLC), an actomyosin contractibility marker, in Th17 and Tγδ17 cells. IL-23-induced RLC phosphorylation required Janus kinase 2 (JAK2) and Rho-associated protein kinase (ROCK) catalytic activity, and further study of the IL-23/ROCK connection revealed an unexpected role of IL-23 in the migration of Tγδ17 and Th17 cells through ROCK activation. In addition, pharmacological inhibition of ROCK reduced Tγδ17 recruitment to inflamed skin upon challenge with inflammatory agent Imiquimod. This work (i) provides new insights into phosphorylation networks that control Th17 cells, (ii) widely expands the current knowledge on IL-23 signaling, and (iii) contributes to the increasing list of immune cells subsets characterized by global phosphoproteomic approaches.

PMID:
32203518
DOI:
10.1371/journal.pbio.3000646
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Conflict of interest statement

"The authors have declared that no competing interests exist."

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