Dicer Insufficiency and MicroRNA-155 Overexpression in Lupus Regulatory T Cells: An Apparent Paradox in the Setting of an Inflammatory Milieu
In: The Journal of Immunology, Jg. 186 (2011-01-15), Heft 2
academicJournal
- 924 - 930
Zugriff:
Systemic lupus erythematosus is a chronic autoimmune disease characterized by loss of tolerance to self-Ags and activation of autoreactive T cells. Regulatory T (Treg) cells play a critical role in controlling the activation of autoreactive T cells. In this study, we investigated mechanisms of potential Treg cell defects in systemic lupus erythematosus using MRL-Fas(lpr/lpr) (MRL/lpr) and MRL-Fas(+/+) mouse models. We found a significant increase in CD4(+)CD25(+)Foxp3(+) Treg cells, albeit with an altered phenotype (CD62L(-)CD69(+)) and with a reduced suppressive capacity, in the lymphoid organs of MRL strains compared with non-autoimmune C3H/HeOuj mice. A search for mechanisms underlying the altered Treg cell phenotype in MRL/lpr mice led us to find a profound reduction in Dicer expression and an altered microRNA (miRNA, miR) profile in MRL/lpr Treg cells. Despite having a reduced level of Dicer, MRL/lpr Treg cells exhibited a significant overexpression of several miRNAs, including let-7a, let-7f, miR-16, miR-23a, miR-23b, miR-27a, and miR-155. Using computational approaches, we identified one of the upregulated miRNAs, miR-155, that can target CD62L and may thus confer the altered Treg cell phenotype in MRL/lpr mice. In fact, the induced overexpression of miR-155 in otherwise normal (C3H/HeOuj) Treg cells reduced their CD62L expression, which mimics the altered Treg cell phenotype in MRL/lpr mice. These data suggest a role of Dicer and miR-155 in regulating Treg cell phenotype. Furthermore, simultaneous appearance of Dicer insufficiency and miR-155 overexpression in diseased mice suggests a Dicer-independent alternative mechanism of miRNA regulation under inflammatory conditions.
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Dicer Insufficiency and MicroRNA-155 Overexpression in Lupus Regulatory T Cells: An Apparent Paradox in the Setting of an Inflammatory Milieu
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Autor/in / Beteiligte Person: | Divekar, Anagha A ; Dubey, Shweta ; Gangalum, Pallavi R ; Singh, Ram Raj |
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Zeitschrift: | The Journal of Immunology, Jg. 186 (2011-01-15), Heft 2 |
Veröffentlichung: | eScholarship, University of California, 2011 |
Medientyp: | academicJournal |
Umfang: | 924 - 930 |
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