Loss of T cell microRNA provides systemic protection against autoimmune pathology in mice

Lei Tian, Gert De Hertogh, Maya Fedeli, Kim A. Staats, Susann Schonefeldt, Stephanie Humblet-Baron, Ludo Van Den Bosch, Paolo Dellabona, James Dooley, Adrian Liston

Research output: Contribution to journalArticle

Abstract

With an increasing number of studies demonstrating alterations in T cell microRNA expression during autoimmune disease, modulation of the T cell microRNA network is considered a potential therapeutic strategy. Due to the complex and often opposing interactions of individual microRNA, prioritization of therapeutic targets first requires dissecting the dominant effects of the T cell microRNA network. Initial results utilizing a unidirectional screen suggested that the tolerogenic functions were dominant, with spontaneous colitis resulting from T cell-specific excision of Dicer. Here we performed a bidirectional screen for microRNA function by removing Dicer from the T cells of both wildtype mice and Transforming Growth Factor β (TGFβ) receptor-deficient mice. This allowed the impact of microRNA loss on T cell activation, effector T cell differentiation and autoimmune pathology to be systematically assessed. This bidirectional screen revealed a dominant immunogenic function for T cell microRNA, with potent suppression of T cell activation, IFNγ production and autoimmune pathology in all targeted organs except the colon, where Dicer-dependent microRNA demonstrated a dominant tolerogenic function. These results reverse the original conclusions of microRNA function in T cells by revealing a systemic pro-autoimmune function.

Original languageEnglish
Pages (from-to)39-48
Number of pages10
JournalJournal of Autoimmunity
Volume38
Issue number1
DOIs
Publication statusPublished - Feb 2012

Keywords

  • Autoimmunity
  • Dicer
  • Immune tolerance
  • MicroRNA
  • T cells

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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    Tian, L., De Hertogh, G., Fedeli, M., Staats, K. A., Schonefeldt, S., Humblet-Baron, S., Van Den Bosch, L., Dellabona, P., Dooley, J., & Liston, A. (2012). Loss of T cell microRNA provides systemic protection against autoimmune pathology in mice. Journal of Autoimmunity, 38(1), 39-48. https://doi.org/10.1016/j.jaut.2011.12.004