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Control of thymic T cell maturation, deletion and egress by the RNA-binding protein HuR.

Publication ,  Journal Article
Papadaki, O; Milatos, S; Grammenoudi, S; Mukherjee, N; Keene, JD; Kontoyiannis, DL
Published in: J Immunol
June 1, 2009

HuR emerged as a posttranscriptional regulator of mRNAs involved in cellular control, stress, and immunity but its role in governing such responses remains elusive. In this study, we assessed HuR's role in the staged progression of thymic T cell differentiation by means of its genetic ablation. Mice with an early deletion of HuR in thymocytes possess enlarged thymi but display a substantial loss of peripheral T cells. We show that this discordant phenotype related to specific defects in thymic cellular processes, which demonstrated HuR's involvement in: 1) intrinsic checkpoint signals suppressing the cell cycle of immature thymocyte progenitors, 2) TCR and antigenic signals promoting the activation and positive selection of mature thymocytes, 3) antigenic and death-receptor signals promoting thymocyte deletion, and 4) chemokine signals driving the egress of postselection thymocytes to the periphery. The cellular consequences of HuR's dysfunction were underlined by the aberrant expression of selective cell cycle regulators, TCR, and death-receptor signaling components. Our studies reveal the signal-dependent context of HuR's cellular activities in thymocytes and its importance in the generation of a physiological T cell pool.

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Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

June 1, 2009

Volume

182

Issue

11

Start / End Page

6779 / 6788

Location

United States

Related Subject Headings

  • Thymus Gland
  • T-Lymphocytes
  • Stem Cells
  • Receptors, Death Domain
  • RNA-Binding Proteins
  • Mice
  • Immunology
  • ELAV-Like Protein 1
  • ELAV Proteins
  • Chemokines
 

Citation

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Papadaki, O., Milatos, S., Grammenoudi, S., Mukherjee, N., Keene, J. D., & Kontoyiannis, D. L. (2009). Control of thymic T cell maturation, deletion and egress by the RNA-binding protein HuR. J Immunol, 182(11), 6779–6788. https://doi.org/10.4049/jimmunol.0900377
Papadaki, Olympia, Stavros Milatos, Sofia Grammenoudi, Neelanjan Mukherjee, Jack D. Keene, and Dimitris L. Kontoyiannis. “Control of thymic T cell maturation, deletion and egress by the RNA-binding protein HuR.J Immunol 182, no. 11 (June 1, 2009): 6779–88. https://doi.org/10.4049/jimmunol.0900377.
Papadaki O, Milatos S, Grammenoudi S, Mukherjee N, Keene JD, Kontoyiannis DL. Control of thymic T cell maturation, deletion and egress by the RNA-binding protein HuR. J Immunol. 2009 Jun 1;182(11):6779–88.
Papadaki, Olympia, et al. “Control of thymic T cell maturation, deletion and egress by the RNA-binding protein HuR.J Immunol, vol. 182, no. 11, June 2009, pp. 6779–88. Pubmed, doi:10.4049/jimmunol.0900377.
Papadaki O, Milatos S, Grammenoudi S, Mukherjee N, Keene JD, Kontoyiannis DL. Control of thymic T cell maturation, deletion and egress by the RNA-binding protein HuR. J Immunol. 2009 Jun 1;182(11):6779–6788.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

June 1, 2009

Volume

182

Issue

11

Start / End Page

6779 / 6788

Location

United States

Related Subject Headings

  • Thymus Gland
  • T-Lymphocytes
  • Stem Cells
  • Receptors, Death Domain
  • RNA-Binding Proteins
  • Mice
  • Immunology
  • ELAV-Like Protein 1
  • ELAV Proteins
  • Chemokines