Reference : Loss of T cell microRNA provides systemic protection against autoimmune pathology in mice
Scientific journals : Article
Human health sciences : Hematology
http://hdl.handle.net/2268/110128
Loss of T cell microRNA provides systemic protection against autoimmune pathology in mice
English
Tian, L. [> >]
De Hertogh, G. [> >]
Fedeli, M. [> >]
Staats, K. A. [> >]
Schonefeldt, S. [> >]
Humblet, Stéphanie mailto [Université de Liège - ULg > > GIGA-R : Hématologie >]
Van Den Bosch, L. [> >]
Dellabona, P. [> >]
Dooley, J. [> >]
Liston, A. [> >]
2012
Journal of Autoimmunity
Academic Press
Yes (verified by ORBi)
International
0896-8411
London
United Kingdom
[en] Dicer ; microRNA ; T cells ; immune tolerance ; autoimmunity
[en] 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 dominanat, 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 functionfor 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.
http://hdl.handle.net/2268/110128

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