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Citations to this article

Phosphorylation of IRF4 by ROCK2 regulates IL-17 and IL-21 production and the development of autoimmunity in mice
Partha S. Biswas, … , Govind Bhagat, Alessandra B. Pernis
Partha S. Biswas, … , Govind Bhagat, Alessandra B. Pernis
Published August 9, 2010
Citation Information: J Clin Invest. 2010;120(9):3280-3295. https://doi.org/10.1172/JCI42856.
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Research Article Autoimmunity Article has an altmetric score of 6

Phosphorylation of IRF4 by ROCK2 regulates IL-17 and IL-21 production and the development of autoimmunity in mice

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Abstract

Deregulated production of IL-17 and IL-21 plays a key pathogenic role in many autoimmune disorders. A delineation of the mechanisms that underlie the inappropriate synthesis of IL-17 and IL-21 in autoimmune diseases can thus provide important insights into potential therapies for these disorders. Here we have shown that the serine-threonine kinase Rho-associated, coiled-coil–containing protein kinase 2 (ROCK2) becomes activated in mouse T cells under Th17 skewing conditions and phosphorylates interferon regulatory factor 4 (IRF4), a transcription factor that is absolutely required for the production of IL-17 and IL-21. We furthermore demonstrated that ROCK2-mediated phosphorylation of IRF4 regulated the synthesis of IL-17 and IL-21 and the differentiation of Th17 cells. Whereas CD4+ T cells from WT mice activated ROCK2 physiologically under Th17 conditions, CD4+ T cells from 2 different mouse models of spontaneous autoimmunity aberrantly activated ROCK2 under neutral conditions. Moreover, administration of ROCK inhibitors ameliorated the deregulated production of IL-17 and IL-21 and the inflammatory and autoantibody responses observed in these autoimmune mice. Our findings thus uncover a crucial link among ROCK2, IRF4, and the production of IL-17 and IL-21 and support the idea that selective inhibition of ROCK2 could represent an important therapeutic regimen for the treatment of autoimmune disorders.

Authors

Partha S. Biswas, Sanjay Gupta, Emily Chang, Li Song, Roslynn A. Stirzaker, James K. Liao, Govind Bhagat, Alessandra B. Pernis

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 Total
Citations: 5 5 7 4 13 12 2 11 16 10 10 6 6 10 9 2 128
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2010 (2)

Title and authors Publication Year
Signal transduction pathways and transcriptional regulation in Th17 cell differentiation
K Hirahara, K Ghoreschi, A Laurence, XP Yang, Y Kanno, JJ O'Shea
Cytokine & Growth Factor Reviews 2010
Aberrant ROCK activation promotes the development of type I diabetes in NOD mice
PS Biswas, S Gupta, E Chang, G Bhagat, AB Pernis
Cellular Immunology 2010

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ISSN: 0021-9738 (print), 1558-8238 (online)

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Referenced in 2 patents
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