IL-23 signaling regulation of pro-inflammatory T-cell migration uncovered by phosphoproteomics
Entity
UAM. Departamento de MedicinaPublisher
Public Library of ScienceDate
2020-03-23Citation
10.1371/journal.pbio.3000646
PLoS Biology 18.3 (2020): e3000646
ISSN
1544-9173 (print); 1545-7885 (online)DOI
10.1371/journal.pbio.3000646Funded by
This work was supported by grants from the Spanish Goverment (Ministry of Economy and Competitiveness). M.N.N, C.A-S, G.P-F, I.R.M and J.P are funded by grants SAF2013-43833-R, SAF2016-78180-R and RYC-2012-10252 to M.N.N. R.C-G and D.C are funded by SAF2014-55579-R to Prof. Sánchez-MadridProject
Gobierno de España. SAF2013-43833-R; Gobierno de España. SAF2016-78180-R; Gobierno de España. RYC-2012-10252; Gobierno de España. SAF2014-55579-REditor's Version
https://doi.org/10.1371/journal.pbio.3000646Subjects
phosphorylation; flow cytometry; T cells; cell migration; lymph nodes; cytokines; inflammatory diseases; interleukins; MedicinaRights
© 2020 Alvarez-Salamero et al.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
Files in this item
Google Scholar:Álvarez-Salamero, Candelas
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Castillo-González, Raquel
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Pastor-Fernández, Gloria
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Mariblanca, Isabel R.
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Pino, Jesús
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Cibrian, Danay
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Navarro, María N.
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