Loss of Functionally Redundant p38 Isoforms in T Cells Enhances Regulatory T Cell Induction.

Autor:	Hayakawa M; From the Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129; the Department of Biochemistry, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan., Hayakawa H; From the Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129; the Department of Biochemistry, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan., Petrova T; the Division of Cell Signalling and Immunology, School of Life Sciences, Wellcome Trust Building, Dundee DD1 5EH, United Kingdom., Ritprajak P; From the Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129; the Department of Microbiology and Immunology and Research Unit of Oral Microbiology, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand., Sutavani RV; the Division of Cell Signalling and Immunology, School of Life Sciences, Wellcome Trust Building, Dundee DD1 5EH, United Kingdom., Jiménez-Andrade GY; From the Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129., Sano Y; From the Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129., Choo MK; From the Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129., Seavitt J; From the Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129., Venigalla RKC; MRC Protein Phosphorylation Unit, School of Life Sciences, Sir James Black Centre, University of Dundee, Dundee DD1 5EH, United Kingdom., Otsu K; the Cardiovascular Division, King's College London, London SE5 9NU, United Kingdom., Georgopoulos K; From the Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129., Arthur JSC; the Division of Cell Signalling and Immunology, School of Life Sciences, Wellcome Trust Building, Dundee DD1 5EH, United Kingdom., Park JM; From the Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129. Electronic address: jmpark@cbrc2.mgh.harvard.edu.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2017 Feb 03; Vol. 292 (5), pp. 1762-1772. Date of Electronic Publication: 2016 Dec 23.
DOI:	10.1074/jbc.M116.764548
Abstrakt:	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. (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)
Databáze:	MEDLINE
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