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Title: Loss of T cell microRNA provides systemic protection against autoimmune pathology in mice
Authors: Tian, Lei
De Hertogh, Gert
Fedeli, Maya
Staats, Kim
Schönefeldt, Susann
Humblet-Baron, Stephanie
Van Den Bosch, Ludo
Dellabona, Paolo
Dooley, James
Liston, Adrian # ×
Issue Date: Feb-2012
Publisher: Academic Press
Series Title: Journal of Autoimmunity vol:38 issue:1 pages:39-48
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.
URI: 
ISSN: 0896-8411
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Research Group Experimental Neurology
Laboratory of Genetics of Autoimmunity
Translational Cell & Tissue Research
Laboratory for Neurobiology (Vesalius Research Center)
× corresponding author
# (joint) last author

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