Foxp3-Dependent MicroRNA155 Confers Competitive Fitness to Regulatory T Cells by Targeting SOCS1 Protein

Li Fan Lu, To Ha Thai, Dinis Pedro Calado, Ashutosh Chaudhry, Masato Kubo, Kentaro Tanaka, Gabriel B. Loeb, Hana Lee, Akihiko Yoshimura, Klaus Rajewsky, Alexander Y. Rudensky

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559 Citations (Scopus)

Abstract

Foxp3+ regulatory T (Treg) cells limit pathogenic immune responses to self-antigens and foreign antigens. An essential role for microRNA (miRNA) in the maintenance and function of Treg cells, revealed by the Treg cell-specific Dicer ablation, raised a question as to a specific miRNA contribution. We found that Foxp3 controlled the elevated miR155 expression required for maintaining Treg cell proliferative activity and numbers under nonlymphopenic conditions. Moreover, miR155 deficiency in Treg cells resulted in increased suppressor of cytokine signaling 1 (SOCS1) expression accompanied by impaired activation of signal transducer and activator of transcription 5 (STAT5) transcription factor in response to limiting amounts of interleukin-2. Our studies suggest that Foxp3-dependent regulation of miR155 maintains competitive fitness of Treg cell subsets by targeting SOCS1, and they provide experimental support for a proposed role for miRNAs in ensuring the robustness of cellular phenotypes.

Original languageEnglish
Pages (from-to)80-91
Number of pages12
JournalImmunity
Volume30
Issue number1
DOIs
Publication statusPublished - 2009 Jan 16

Keywords

  • CELLIMMUNO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Lu, L. F., Thai, T. H., Calado, D. P., Chaudhry, A., Kubo, M., Tanaka, K., Loeb, G. B., Lee, H., Yoshimura, A., Rajewsky, K., & Rudensky, A. Y. (2009). Foxp3-Dependent MicroRNA155 Confers Competitive Fitness to Regulatory T Cells by Targeting SOCS1 Protein. Immunity, 30(1), 80-91. https://doi.org/10.1016/j.immuni.2008.11.010