Altered miRNA expression in T regulatory cells in course of multiple sclerosis.
J Neuroimmunol
; 226(1-2): 165-71, 2010 Sep 14.
Article
en En
| MEDLINE
| ID: mdl-20637509
ABSTRACT
OBJECTIVES:
Multiple sclerosis (MS) is a chronic inflammatory response against constituents of the central nervous system. It is known that regulatory T cells (Tregs) play a key role in the autoimmune balance and their improper function may facilitate the expansion of autoaggressive T cell clones. Recently, microRNAs (miRNAs) have been involved in autoimmune disorders and their loss-of-function in immune cells was shown to facilitate systemic autoimmune disorders. Here, we analyzed the miRNA expression profile in Tregs from MS-RR.METHODS:
We assessed miRNA genome-wide expression profile by microarray analysis on CD4(+)CD25(+high) T cells from 12 MS relapsing-remitting patients in stable condition and 14 healthy controls. Since CD4(+)CD25(+high) T cells comprise both T regulatory cells (CD4(+)CD25(+high)CD127(dim/-)) and T effector cells (CD4(+)CD25(+high)CD127(+)), we performed a quantitative RT-PCR on CD4(+)CD25(+high)CD127(dim/-) and CD4(+)CD25(+high)CD127(+) cells isolated from the same blood sample.RESULTS:
We found 23 human miRNAs differentially expressed between CD4(+)CD25(high)bona fide Treg cells from MS patients vs. healthy donors, but, conversely, among the deregulated miRNAs, members of the miR-106b-25 were found down-regulated in MS patients when compared to healthy donors in CD4(+)CD25(high)CD127(dim/-) T regulatory cells. More interesting, the ratio between Treg/Teff showed an enrichment of these microRNA in T regulatory cells derived from patients if compared to healthy controls.CONCLUSION:
miR-106b and miR-25 were previously shown to modulate the TGF-ß signaling pathway through their action on CDKN1A/p21 and BCL2L11/Bim. TGF-ß is involved in T regulatory cells differentiation and maturation. Therefore, the deregulation of this miRNA cluster may alter Treg cells activity in course of MS, by altering TGF-ß biological functions.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Regulación de la Expresión Génica
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Linfocitos T Reguladores
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MicroARNs
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Esclerosis Múltiple
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Neuroimmunol
Año:
2010
Tipo del documento:
Article
País de afiliación:
Italia