Loss of functionally redundant p38 isoforms in T cells enhances regulatory T cell induction

Morisada Hayakawa, Hiroko Hayakawa, Tsvetana Petrova, Patcharee Ritprajak, Ruhcha V. Sutavani, Guillermina Yanek Jimenez-Andrade, Yasuyo Sano, Min-Kyung Choo, John Seavitt, Ram K. C. Venigalla, Kinya Otsu, Katia Georgopoulos, J. Simon C. Arthur, Jin Mo Park (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)
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The evolutionarily conserved protein kinase p38 mediates innate resistance to environmental stress and microbial infection. Four p38 isoforms exist in mammals and may have been co-opted for new roles in adaptive immunity. Murine T cells deficient in p38α, the ubiquitously expressed p38 isoform, showed no readily apparent cell-autonomous defects while expressing elevated amounts of another isoform, p38β. Mice with T cells simultaneously lacking p38α and p38β displayed lymphoid atrophy and elevated Foxp3+ regulatory T cell frequencies. Double deficiency of p38α and p38β in naïve CD4+ T cells resulted in an attenuation of MAPK-activated protein kinase (MK)-dependent mTOR signaling after T cell receptor engagement, and enhanced their differentiation into regulatory T cells under appropriate inducing conditions. Pharmacological inhibition of the p38-MK-mTOR signaling module produced similar effects, revealing potential for therapeutic applications.
Original languageEnglish
Pages (from-to)1762-1772
Number of pages11
JournalJournal of Biological Chemistry
Issue number5
Early online date23 Dec 2016
Publication statusPublished - 3 Feb 2017


  • P-38
  • T-Cell
  • Signal transduction
  • Immunology
  • Mouse


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