Suppressive regulatory T cell activity is potentiated by glycogen synthase kinase 3β inhibition

Jay A. Graham, Michael Fray, Stephanie De Haseth, Kang Mi Lee, Moh Moh Lian, Catharine M. Chase, Joren C. Madsen, James Markmann, Gilles Benichou, Robert B. Colvin, A. Benedict Cosimi, Shaoping Deng, James Kim, Alessandro Alessandrini

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The mechanism by which regulatory T (Treg) cells suppress the immune response is not well defined. A recent study has shown that β-catenin prolongs Treg cell survival. Because β-catenin is regulated by glycogen synthase kinase 3β (GSK-3β)-directed phosphorylation, we focused on GSK-3β and the role it plays in Treg cell function. Inhibition of GSK-3β led to increased suppression activity by Treg cells. Inhibitor-treated Treg cells exhibited prolonged FoxP3 expression and increased levels of β-catenin and of the antiapoptotic protein Bcl-xL. Systemic administration of GSK-3β inhibitor resulted in prolonged islet survival in an allotransplant mouse model. Our data suggest that GSK-3β could be a useful target in developing strategies designed to increase the stability and function of Treg cells for inducing allotransplant tolerance or treating autoimmune conditions.

Original languageEnglish (US)
Pages (from-to)32852-32859
Number of pages8
JournalJournal of Biological Chemistry
Volume285
Issue number43
DOIs
StatePublished - Oct 22 2010
Externally publishedYes

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Glycogen Synthase Kinase 3
T-cells
Regulatory T-Lymphocytes
Catenins
Phosphorylation
Cells
Cell Survival
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Graham, J. A., Fray, M., De Haseth, S., Lee, K. M., Lian, M. M., Chase, C. M., ... Alessandrini, A. (2010). Suppressive regulatory T cell activity is potentiated by glycogen synthase kinase 3β inhibition. Journal of Biological Chemistry, 285(43), 32852-32859. https://doi.org/10.1074/jbc.M110.150904

Suppressive regulatory T cell activity is potentiated by glycogen synthase kinase 3β inhibition. / Graham, Jay A.; Fray, Michael; De Haseth, Stephanie; Lee, Kang Mi; Lian, Moh Moh; Chase, Catharine M.; Madsen, Joren C.; Markmann, James; Benichou, Gilles; Colvin, Robert B.; Cosimi, A. Benedict; Deng, Shaoping; Kim, James; Alessandrini, Alessandro.

In: Journal of Biological Chemistry, Vol. 285, No. 43, 22.10.2010, p. 32852-32859.

Research output: Contribution to journalArticle

Graham, JA, Fray, M, De Haseth, S, Lee, KM, Lian, MM, Chase, CM, Madsen, JC, Markmann, J, Benichou, G, Colvin, RB, Cosimi, AB, Deng, S, Kim, J & Alessandrini, A 2010, 'Suppressive regulatory T cell activity is potentiated by glycogen synthase kinase 3β inhibition', Journal of Biological Chemistry, vol. 285, no. 43, pp. 32852-32859. https://doi.org/10.1074/jbc.M110.150904
Graham, Jay A. ; Fray, Michael ; De Haseth, Stephanie ; Lee, Kang Mi ; Lian, Moh Moh ; Chase, Catharine M. ; Madsen, Joren C. ; Markmann, James ; Benichou, Gilles ; Colvin, Robert B. ; Cosimi, A. Benedict ; Deng, Shaoping ; Kim, James ; Alessandrini, Alessandro. / Suppressive regulatory T cell activity is potentiated by glycogen synthase kinase 3β inhibition. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 43. pp. 32852-32859.
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